Adamax

Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions.

Therapeutic peptides are emerging as promising adjuncts in the management of orthopaedic injuries, grounded in their ability to modulate molecular signaling networks central to cellular medicine. By acting on key pathways such as PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK, peptides exert influence over tissue regeneration, inflammation resolution, and neuromuscular recovery. Wound-healing peptides such as BPC-157, TB-500, and GHK-Cu promote angiogenesis, integrin-mediated extracellular matrix remodeling, and fibroblast activation, whereas growth hormone secretagogues like ipamorelin, CJC-1295, tesamorelin, sermorelin, and AOD-9604 activate IGF-1 signaling and satellite cell repair. Recovery-enhancing agents such as epithalon, delta sleep-inducing peptide, and pinealon target circadian and mitochondrial regulators, and neuroactive peptides like selank, semax, and dihexa enhance brain-derived neurotrophic factor and HGF/c-Met pathways critical to neuroplasticity. Although preclinical studies are promising, there is a current lack of clinical trials. This review integrates current mechanistic insights with orthopaedic relevance, emphasizing safety, efficacy, and future directions for responsible integration into musculoskeletal care.

Semax peptide targets the μ opioid receptor gene Oprm1 to promote deubiquitination and functional recovery after spinal cord injury in female mice.

Lysosomal membrane permeabilization (LMP) is exacerbated following spinal cord injury (SCI), leading to increased neuronal cell death. Ubiquitination may affect LMP by regulating the stability and functionality of lysosomal membranes. Semax, a synthetic heptapeptide, comprising the ACTH (4-7) fragment and a C-terminal Pro-Gly-Pro tripeptide, exhibits neuroprotective properties and improves cognitive function. Given the key roles of LMP and ubiquitination in SCI pathophysiology, this study investigated how Semax could modulate these pathways to affect functional recovery following SCI. An SCI mouse model was generated by impacting the spinal cord of female C57BL/6 mice at T9-T10. Functional recovery in SCI mice was evaluated using histochemical methods, along with footprint analysis, Basso scores and inclined plane tests. Marker levels and distributions in the SCI model and in the PC12 cell neuroinflammation model were analysed using immunofluorescence, Western blot, RT-qPCR and transmission electron microscopy. RNA sequencing, network pharmacology and molecular docking were used to identify possible molecular targets of Semax. Semax improved SCI functional recovery and inhibited LMP-related pyroptosis in SCI mice and neuroinflammation models, by decreasing oxidative stress. RNA-seq and other analyses found that Semax regulated the ubiquitin specific protease USP18. USP18 knockdown confirmed Semax's role in SCI recovery. Network pharmacology and docking revealed the μ-opioid receptor as a Semax target. Semax promoted SCI functional recovery by targeting μ-opioid receptors, which regulated USP18 and, subsequently, deubiquitination of the fat mass and obesity-associated protein (FTO), suggesting its potential for SCI treatment.

Pharmacological Aspects of Neuro-Immune Interactions.

The use of systematic approach for the analysis of mechanism of action of drugs at different levels of biological organization of organisms is an important task in experimental and clinical pharmacology for drug designing and increasing the efficacy and safety of drugs. The analysis of published data on pharmacological effects of psychotropic drugs possessing immunomodulatory and/or antiviral properties have shown a correlation between central effects of examined drugs associated with the impact on the processes of neurogenesis of adult brain and survival of neurons, and their ability to alter levels of key proinflammatory cytokines. The changes that occur as a result of the influence of pharmacological agents at one of the systems should inevitably lead to the functional reorganization at another. Integrative mechanisms underlying the neuro-immune interactions may explain the "pleiotropic" pharmacological effects of some antiviral and immunomodulatory drugs. Amantadine, which was originally considered as an antiviral agent, was approved as anti-parkinsonic drug after its wide medical use. The prolonged administration of interferon alpha caused depression in 30-45% of patients, thus limiting its clinical use. The antiviral drug "Oseltamivir" may provoke the development of central side effects, including abnormal behavior, delirium, impaired perception and suicides. Anti-herpethetical drug "Panavir" shows pronounced neuroprotective properties. The purpose of this review is to analyze the experimental and clinical data related to central effects of drugs with antiviral or/and immunotropic activity, and to discover the relationship of these effects with changes in reactivity of immune system and proinflammatory response.

Mine Gas Concentration Forecasting Model Based on an Optimized BiGRU Network.

To improve the utilization of mine gas concentration monitoring data with deep learning theory, we propose a gas concentration forecasting model with a bidirectional gated recurrent unit neural network (Adamax-BiGRU) using an adaptive moment estimation maximum (Adamax) optimization algorithm. First, we apply the Laida criterion and Lagrange interpolation to preprocess the gas concentration monitoring data. Then, the MSE is used as the loss function to determine the parameters of the hidden layer, hidden nodes, and iterations of the BiGRU model. Finally, the Adamax algorithm is used to optimize the BiGRU model to forecast the gas concentration. The experimental results show that compared with the recurrent neural network, LSTM, and gated recurrent unit (GRU) models, the error of the BiGRU model on the test set is reduced by 25.58, 12.53, and 3.01%, respectively. Compared with other optimization algorithms, the Adamax optimization algorithm achieved the best forecasting results. Thus, Adamax-BiGRU is an effective method to predict gas concentration values and has a good application value.

ACTH-like Peptides Compensate Rat Brain Gene Expression Profile Disrupted by Ischemia a Day After Experimental Stroke.

Background: Ischemic stroke results from a disruption of cerebral blood flow. Adrenocorticotropic hormone (ACTH) serves as the basis for the creation of synthetic peptides as neuroprotective agents for stroke therapy. Previously, using RNA-Seq we first revealed differential expressed genes (DEGs) associated with ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP peptides under cerebral ischemia conditions. Analysis was carried out at 4.5 h after transient middle cerebral artery occlusion (tMCAO) model in the ipsilateral frontal cortex of a rat brain. Methods: Here, we analyzed the penumbra-associated frontal cortex of rats and actions under the same peptides at 24 h after tMCAO using RNA-Seq. Results: 3774 DEGs (fold change > 1.5 and Padj < 0.05) were identified under ischemia conditions, whereas 1539 and 2066 DEGs were revealed under Semax and ACTH(6-9)PGP peptides at 24 h after tMCAO. Furthermore, both peptides significantly reduced expression distortions caused by ischemia for 1171 genes associated with immune and neurosignaling pathways. Concomitantly, there were 32 DEGs under ACTH(6-9)PGP versus Semax administration at 24 h after tMCAO. Besides, neurogenesis-, angiogenesis-, protein kinase- and growth factor-related DEGs were revealed under peptides action. Previously, we observed the neuroprotective effect of peptides at the histological level in rat brains at 24 h after tMCAO. Thus, here we demonstrate the transcriptome manifestation of this histological effect. Furthermore, comparison with previous data at the 4.5 h post-tMCAO time point showed that the pattern of peptide action on the transcriptome depends on the time elapsed after tMCAO. Conclusions: We revealed that the effect of ACTH(6-9)PGP was more similar to Semax than different from it a day after tMCAO. At this time point, ACTH-like peptides compensated rat brain gene expression profiles disrupted by ischemia. Thus, our results may be useful for selecting more effective structures for future anti-stroke drugs and appropriate post-stroke time points for their testing.

Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models.

Alzheimer's disease, the most common form of dementia, is characterized by the aggregation of amyloid beta protein (A&#x3b2;). The aggregation and toxicity of A&#x3b2; are strongly modulated by metal ions and phospholipidic membranes. In particular, Cu2+ ions play a pivotal role in modulating A&#x3b2; aggregation. Although in the last decades several natural or synthetic compounds were evaluated as candidate drugs, to date, no treatments are available for the pathology. Multifunctional compounds able to both inhibit fibrillogenesis, and in particular the formation of oligomeric species, and prevent the formation of the A&#x3b2;:Cu2+ complex are of particular interest. Here we tested the anti-aggregating properties of a heptapeptide, Semax, an ACTH-like peptide, which is known to form a stable complex with Cu2+ ions and has been proven to have neuroprotective and nootropic effects. We demonstrated through a combination of spectrofluorometric, calorimetric, and MTT assays that Semax not only is able to prevent the formation of A&#x3b2;:Cu2+ complexes but also has anti-aggregating and protective properties especially in the presence of Cu2+. The results suggest that Semax inhibits fiber formation by interfering with the fibrillogenesis of A&#x3b2;:Cu2+ complexes.

Enhancing accuracy in brain stroke detection: Multi-layer perceptron with Adadelta, RMSProp and AdaMax optimizers.

The human brain is an extremely intricate and fascinating organ that is made up of the cerebrum, cerebellum, and brainstem and is protected by the skull. Brain stroke is recognized as a potentially fatal condition brought on by an unfavorable obstruction in the arteries supplying the brain. The severity of brain stroke may be reduced or controlled with its early prognosis to lessen the mortality rate and lead to good health. This paper proposed a technique to predict brain strokes with high accuracy. The model was constructed using data related to brain strokes. The aim of this work is to use Multi Layer Perceptron (MLP) as a classification technique for stroke data and used multi-optimizers that include Adaptive moment estimation with Maximum (AdaMax), Root Mean Squared Propagation (RMSProp) and Adaptive learning rate method (Adadelta). The experiment shows RMSProp optimizer is best with a data training accuracy of 95.8% and a value for data testing accuracy of 94.9%. The novelty of work is to incorporate multiple optimizers alongside the MLP classifier which offers a comprehensive approach to stroke prediction, providing a more robust and accurate solution. The obtained results underscore the effectiveness of the proposed methodology in enhancing the accuracy of brain stroke detection, thereby paving the way for potential advancements in medical diagnosis and treatment.

Therapeutic peptides in gerontology: mechanisms and applications for healthy aging.

Peptide therapeutics represent an emerging frontier in gerontological medicine, targeting fundamental hallmarks of aging including metabolic dysfunction, telomere attrition, tissue repair impairment, and hormonal decline. To comprehensively review the mechanisms, clinical applications, evidence base, and safety profiles of therapeutic peptides with demonstrated or potential applications in healthy aging and age-related conditions. A comprehensive narrative review was conducted through systematic searches of PubMed, Scopus, and regulatory databases (FDA, WADA) from inception through January 2026. Search terms included "peptide therapeutics," "aging," "gerontology," "healthspan," combined with specific peptide names (tirzepatide, epitalon, GHK-Cu, BPC-157, TB-500, Semax, CJC-1295, ipamorelin, bremelanotide). Peer-reviewed articles, clinical trials, regulatory documents, and preclinical studies were evaluated. A total of 20 primary sources were selected based on relevance, methodological quality, and contribution to understanding peptide mechanisms and clinical outcomes in aging populations. Nine peptides were identified spanning diverse aging interventions: metabolic restoration (tirzepatide), telomere biology (epitalon), dermal regeneration (GHK-Cu), tissue repair (BPC-157, TB-500), neuroprotection (Semax), growth hormone modulation (CJC-1295, ipamorelin), and sexual function (bremelanotide). FDA-approved agents demonstrated robust safety profiles from large-scale trials. Non-approved peptides showed promising preclinical and limited clinical evidence but lack long-term safety data and systematic validation. Significant knowledge gaps include optimal dosing regimens, combination therapy effects, and biomarkers for monitoring efficacy. Therapeutic peptides offer mechanistically diverse approaches to multiple aging hallmarks. While FDA-approved agents demonstrate clinical potential, investigational peptides require rigorous validation through well-designed clinical trials to establish safety and efficacy for healthspan extension.

Influence of the N-terminus acetylation of Semax, a synthetic analog of ACTH(4-10), on copper(II) and zinc(II) coordination and biological properties.

Semax is a heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro) that encompasses the sequence 4-7 of N-terminal domain of the adrenocorticotropic hormone and a C-terminal Pro-Gly-Pro tripeptide. N-terminal amino group acetylation (Ac-Semax) modulates the chemical and biological properties of parental peptide, modifying the ability of Semax to form complex species with Cu(II) ion. At physiological pH, the main complex species formed by Ac-Semax, [CuLH-2]2-, consists in a distorted CuN3O chromophore with a weak apical interaction of the methionine sulphur. Such a complex differs from the Cu(II)-Semax complex system, which exhibits a CuN4 chromophore. The reduced ligand field affects the [CuLH-2]2- formal redox potential, which is more positive than that of Cu(II)-Semax corresponding species. In the amino-free form, the resulting complex species is redox-stable and unreactive against ascorbic acid, unlike the acetylated form. Semax acetylation did not protect from Cu(II) induced toxicity on a SH-SY5Y neuroblastoma cell line, thus demonstrating the crucial role played by the free NH2 terminus in the cell protection. Since several brain diseases are associated either to Cu(II) or Zn(II) dyshomeostasis, here we characterized also the complex species formed by Zn(II) with Semax and Ac-Semax. Both peptides were able to form Zn(II) complex species with comparable strength. Confocal microscopy imaging confirmed that peptide group acetylation does not affect the Zn(II) influx in neuroblastoma cells. Moreover, a punctuate distribution of Zn(II) within the cells suggests a preferred subcellular localization that might explain the zinc toxic effect. A future perspective can be the use of Ac-Semax as ionophore in antibody drug conjugates to produce a dysmetallostasis in tumor cells.

Indoor surface classification for mobile robots.

The ability to recognize the surface type is crucial for both indoor and outdoor mobile robots. Knowing the surface type can help indoor mobile robots move more safely and adjust their movement accordingly. However, recognizing surface characteristics is challenging since similar planes can appear substantially different; for instance, carpets come in various types and colors. To address this inherent uncertainty in vision-based surface classification, this study first generates a new, unique data set composed of 2,081 surface images (carpet, tiles, and wood) captured in different indoor environments. Secondly, the pre-trained state-of-the-art deep learning models, namely InceptionV3, VGG16, VGG19, ResNet50, Xception, InceptionResNetV2, and MobileNetV2, were utilized to recognize the surface type. Additionally, a lightweight MobileNetV2-modified model was proposed for surface classification. The proposed model has approximately four times fewer total parameters than the original MobileNetV2 model, reducing the size of the trained model weights from 42 MB to 11 MB. Thus, the proposed model can be used in robotic systems with limited computational capacity and embedded systems. Lastly, several optimizers, such as SGD, RMSProp, Adam, Adadelta, Adamax, Adagrad, and Nadam, are applied to distinguish the most efficient network. Experimental results demonstrate that the proposed model outperforms all other applied methods and existing approaches in the literature by achieving 99.52% accuracy and an average score of 99.66% in precision, recall, and F1-score. In addition to this, the proposed lightweight model was tested in real-time on a mobile robot in 11 scenarios consisting of various indoor environments such as offices, hallways, and homes, resulting in an accuracy of 99.25%. Finally, each model was evaluated in terms of model loading time and processing time. The proposed model requires less loading and processing time than the other models.

Modulation of neuropathological pathways by bioactive peptides and proteins/polypeptides: Targeting oxidative stress in neurodegenerative diseases.

Neurodegenerative disorders (NDDs) pose a growing global health burden, primarily due to their progressive nature and the limited efficacy of existing treatments. Bioactive peptides and proteins/polypeptides, particularly those derived from dietary and natural sources, show promise in modulating neurobiological pathways central to neurodegeneration. This review aims to critically examine the neuroprotective roles of Bioactive peptides and proteins/polypeptides in NDDs, elucidating their mechanisms of action, potential therapeutic applications in conditions like Alzheimer's, Parkinso's disease, Huntington's disease, and others, as well as the trends in peptide-based therapeutics. Bioactive peptides and proteins/polyspeptides, such as NGF, BDNF, GDNF, Semax, and Exendin-4, have been found to modulate several critical mechanisms, including the reduction of oxidative stress (OS), inhibition of neuroinflammation, preservation of mitochondria, and enhancement of synaptic plasticity. These peptides have demonstrated efficacy in preclinical and early-phase clinical trials across a spectrum of NDDs. Delivery challenges, such as blood-brain barrier (BBB) permeability and enzymatic degradation, have been acknowledged. Ongoing innovations in peptide engineering, nanoparticle-based delivery systems, CRISPR-assisted design, and AI-driven screening are addressing these limitations. By targeting multiple pathogenic mechanisms simultaneously, peptide-based therapeutics present a rational and innovative approach to NDD management. Their multifunctional action profiles and ability to target specific molecular pathways highlight their potential as next-generation neuroprotective agents. However, future clinical validation and advanced strategies are essential for translating these promising molecules into effective treatments.

Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia.

Consisting of a fragment of ACTH(4-7) and C-terminal PGP tripeptide, the polypeptide Semax is successfully used for acute stroke therapy. Previous experiments showed rapid induction of Bdnf, Ngf, and TrkB expression in intact rat hippocampus following Semax treatment. To investigate the mRNA expression of neurotrophins and their receptors after treatment with either Semax or PGP, the rat brains were analyzed at three time points following a permanent middle cerebral artery occlusion (pMCAO). We have shown for the first time that both Semax and PGP activate the transcription of neurotrophins and their receptors in the cortex of rats subjected to pMCAO. The profiles of transcription alteration under PGP and Semax treatment were partially overlapped. Semax enhanced the transcription of Bdnf, TrkC, and TrkA 3 h after occlusion, Nt-3 and Ngf 24 h after occlusion, and Ngf 72 h after occlusion. PGP enhanced the transcription of Bdnf and TrkC 3 h after pMCAO and Ngf, TrkB, TrkC, and TrkA 24 h after pMCAO. The analysis of the transcription alterations under PGP and Semax treatment in the cortex of rats without surgery, sham-operated rats and rats subjected to pMCAO revealed that Semax selectively affected the transcription of neurotrophins and their receptors in the ischemic rat cortex, whereas the influence of PGP was mainly unspecific.

The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis.

The nootropic neuroprotective peptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) has proved efficient in the therapy of brain stroke; however, the molecular mechanisms underlying its action remain obscure. Our genome-wide study was designed to investigate the response of the transcriptome of ischemized rat brain cortex tissues to the action of Semax in vivo. The gene-expression alteration caused by the action of the peptide Semax was compared with the gene expression of the "ischemia" group animals at 3 and 24 h after permanent middle cerebral artery occlusion (pMCAO). The peptide predominantly enhanced the expression of genes related to the immune system. Three hours after pMCAO, Semax influenced the expression of some genes that affect the activity of immune cells, and, 24 h after pMCAO, the action of Semax on the immune response increased considerably. The genes implicated in this response represented over 50% of the total number of genes that exhibited Semax-induced altered expression. Among the immune-response genes, the expression of which was modulated by Semax, genes that encode immunoglobulins and chemokines formed the most notable groups. In response to Semax administration, 24 genes related to the vascular system exhibited altered expression 3 h after pMCAO, whereas 12 genes were changed 24 h after pMCAO. These genes are associated with such processes as the development and migration of endothelial tissue, the migration of smooth muscle cells, hematopoiesis, and vasculogenesis. Semax affects several biological processes involved in the function of various systems. The immune response is the process most markedly affected by the drug. Semax altered the expression of genes that modulate the amount and mobility of immune cells and enhanced the expression of genes that encode chemokines and immunoglobulins. In conditions of rat brain focal ischemia, Semax influenced the expression of genes that promote the formation and functioning of the vascular system.The immunomodulating effect of the peptide discovered in our research and its impact on the vascular system during ischemia are likely to be the key mechanisms underlying the neuroprotective effects of the peptide.

Effective skin cancer classification by modified and optimized inception-ResNet-V2 model.

Artificial Intelligence tools are flourishing in biomedical diagnosis, particularly in oncology. The prediction of skin cancer from dermoscopic images using deep learning neural networks has gained importance in recent years because of their inherent early non-invasive diagnostic capabilities. This study presents the results of the classification of benign nevus and malignant melanoma lesions using a deep learning model. The model incorporates an efficient pre-processing stage powered by median filtering and a class-balancing stage powered by the Synthetic Minority Oversampling Technique (SMOTE) to improve classification results. First, the classification efficiency of four pre-trained models, namely, ResNet50, EfficientNet B0, Inception-V3, and Inception-ResNet-V2, were studied, and the results revealed that they achieved accuracies of 93.90%, 94.37%, 94.87%, and 95.77%, respectively. Second, the effect of optimization and hyperparameter tuning on the Inception-ResNet-V2 model is studied considering Adam, Nadam, and AdaMax optimizers, with fivefold cross validation. The experimental results revealed that the AdaMax optimizer with validation achieved an overall consistent performance with accuracy, sensitivity, and specificity of 97.65%, 96.67%, and 98.92%, respectively. The results support the efficacy of the model in predicting skin cancer malignancy; thus, its integration into clinical practice could benefit healthcare services.

Functional Connectomic Approach to Studying Selank and Semax Effects.

The present study was aimed at the assessment of effects of anxiolytic Selank and nootropic Semax on the whole-brain resting-state functional connectivity (FC) of each of the predefined regions of interest (ROIs) in 52 healthy participants. The ROIs included amygdala (one of the key regions for the regulation of anxiety) and dorsolateral prefrontal cortex (DLPFC; the key region for executive functions, including working memory) in the right and left hemisphere. Resting-state fMRI was carried out three times, namely before, after 5 and 20 min of the injection of either Semax, or Selank, or placebo. Between-group alongwith between-condition differences were revealed in FC between the right amygdala and a region in fusiform, inferior and middle temporal as well as parahippocampal gyri in the right hemisphere. Post hoc analysis allowed us to define both general and specific effects of Selank and Semax on FC between the right amygdala and the right temporal cortex for the first time.

[Evolution of the stress concept].

New aspects of the classical Selye stress theory are considered. Stress is interpreted as a systemic response of the organism. In the last years the stress concept h as undergone transformation to the notion of emotional stress. In the context of the theory of functional systems, emotional stress is regarded as developing in the so-called conflict situations in which the participating subjects are unable to achieve useful adaptive goals. The primary cerebral mechanisms of emotional stress and the role played by neuromediators and neuropeptides are discussed. Dynamics of impairment of various functional systems under stressful conditions is discussed with special emphasis on individual tolerance to emotional stress and the role of oligopeptides (substance P), delta sleep inducing peptide, beta-endorphin and semax as antistress factors increasing resistance to stressful impacts.

Sigmoidal maximal effect modeling of low-density lipoprotein cholesterol concentration and annual incidence of coronary heart disease events in secondary prevention trials.

To evaluate the relationship between low-density lipoprotein cholesterol (LDL-C) concentration and the annual incidence of combined coronary heart disease (CHD) events&#x2014;death or nonfatal myocardial infarction (NFMI)&#x2014;by using sigmoidal maximal effect (sEmax) modeling of published data in various populations at risk for CHD events, and to use the best performing sEmax model generated to calculate the number needed to treat (NNT) to prevent a single CHD death or NFMI event across a range of LDL-C concentrations. Literature-based modeling analysis. A total of 95,955 patients from 22 published cardiovascular secondary prevention trials. Four distinct sEmax models were created based on intervention approach and CHD event risk for each trial population. Model outputs included the following: Emax (maximum CHD death/NFMI rate), E0 (minimum CHD death/NFMI rate), and fit parameters. The best-fitting sEmax model was compared with linear, log-linear, and logit models, and it was used for calculation of annualized NNT to prevent one CHD death or NFMI event with statins. The best fitting sEmax model was constructed from nine statin intervention trials in 60,483 clinically stable patients with CHD or CHD risk equivalents (Emax = 4.84%/year [95% confidence interval (CI) 4.11&#x2013;5.41%/year], E0 = 1.24%/year [95% CI 0.64&#x2013;1.83%/year]) and was superior to linear, log-linear, and logit models. Reduction of CHD death/NFMI incidence diminished at an LDL-C level near 90 mg/dl and became near static at an LDL-C level of 60&#x2013;70 mg/dl. Annual NNT for LDL-C reduction from a baseline of 130&#x2013;100 mg/dl, 90, and 70 mg/dl was 129, 104, and 83, respectively, and from a baseline of 100&#x2013;70 mg/dl was 232. An sEmax model fully characterized the relationship between LDL-C concentration and incidence of CHD death or NFMI in a high-risk population receiving statins, with diminishing event reduction at an LDL-C level less than 90 mg/dl, and limited projected event reduction beyond an LDL-C level of ~60&#x2013;70 mg/dl. As baseline LDL-C level declines, the NNT sharply increases.

Artificial Intelligence-based fine-tuning model for fall activity recognition in disabled persons within an IoT environment.

Remote monitoring of fall actions or conditions and the everyday lifecycle of disabled losses is the vital drive of current telemedicine. The Internet of Things (IoT) and Artificial Intelligence (AI) models, which incorporate deep learning (DL) and machine learning (ML) techniques, are increasingly applied in healthcare to automate the detection of abnormal and unhealthy conditions. Fall detection (FD) in elderly patients and human action recognition for surveillance are crucial for safety, but achieving high accuracy remains challenging due to complex human movements. Detecting falls is crucial for healthcare and well-being. This paper presents a novel Temporal Convolutional Network-Based Fall Activity Recognition System for Disabled Persons (TCN-FARSDP) technique designed for use in an IoT Environment. The aim is to monitor and detect fall incidents among disabled persons. Initially, the TCN-FARSDP method performs the image pre-processing stage using Gaussian filtering (GF) to eliminate noise and improve the image clarity. Next, the fusion of feature extraction models involves three techniques: NASNetMobile, DenseNet121, and MobileNetV3Large. For the detection of fall activities, the temporal convolutional network (TCN) classifier is employed. Finally, fine-tuning is performed using the Adamax to enhance the convergence and stability of the model. The performance evaluation of the TCN-FARSDP approach is implemented under an FD dataset. The experimental validation of the TCN-FARSDP approach portrayed a superior accuracy value of 99.48% over existing techniques.

Effects of Semax on the Default Mode Network of the Brain.

The effects of nootropic drug Semax on the neuronal network of the brain were studied by the resting state functional magnetic-resonance imaging (resting state fMRI). The study was carried out on two groups of healthy volunteers (11 men and 13 women aged 43.9&#xb1;9.5 years). Resting state fMRI was carried out 3 times: directly before and 5 and 20 min after intranasal 1% Semax (14 subjects) or placebo (10 subjects). The topography of the resting state default mode network was studied. A greater volume of the default mode network rostral (medial frontal cortex) subcomponent was detected in the Semax group in comparison with controls. Resting state fMRI confirmed Semax effects on the neuronal network of the brain and demonstrated topography of these effects.

[The efficacy of semax in the tretament of patients at different stages of ischemic stroke].

To evaluate the efficacy of semax and timing of rehabilitation on the dynamics of plasma BDNF levels, motor performance, and Barthel index score in patients after ischemic stroke (IS). One hundred and ten patients after IS (43 men, 67 women, mean age 58.0&#xb1;9.7, &#x41c;&#x435; 63 years) were examined. All patients were divided into early (89&#xb1;9 days) and late (214&#xb1;22 days) rehabilitation groups. Each group was subdivided into semax+ and semax- subgroups. Standard regimen of semax included 2 courses (6000 mcg/day) for 10 days with 20 day interval. Plasma BDNF levels, motor performance on the British Medical Research Council scale and Barthel index were assessed in all groups. Administration of semax, regardless of the timing of rehabilitation, increased BDNF plasma levels which remained high during the whole study period. In semax- subgroups high BDNF plasma levels were positively correlated with early rehabilitation. Administration of semax and high BDNF levels accelerated the improvement and ameliorated the final outcome of Barthel score index. There was a positive correlation between BDNF plasma levels and Barthel score, as well as a correlation between early rehabilitation and motor performance improvement. The correlation between BDNF plasma levels and Barthel score was modified by the timing of rehabilitation. Early rehabilitation and administration of semax increase BDNF plasma level, speed functional recovery, and improve motor performance.

[POSSIBLE ROLE OF TRANSTHYRETIN IN THE BIOLOGICAL MECHANISM OF THE REGULATORY PEPTIDE NEUROPROTECTION.].

The peptide preparation Semax has been effectively used for therapy of ischemic stroke. However, the mechanisms of its action are insufficiently understood and actively studied. The full-genome analysis of the transcriptome implemented in our recent work dem- onstrated that under conditions of focal ischemia of rat brain the Semax modified the profile of the transcription activity of many genes. In this case, the difference in the transcription levels of the gene encoding the protein transthyretin (Ttr) expression in rats under the pathological conditions of ischemia and in the presence of Semax was very high. High similarity between the effects of Ttr and coupled molecular systems with the Semax effects in ischemic stroke allowed us to suggest that the neuroprotection mechanisms of Semax (and, possibly, of other neuroprotection mechanisms of Semax) could be mediated by Ttr. In this review, we discussed the role of Ttr in CNS and its possible role in the neuroprotection mechanism of Semax.

Semax, synthetic ACTH(4-10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats.

Selective serotonin reuptake inhibitors (SSRI) are commonly used to treat depression during pregnancy. SSRIs cross the placenta and may influence the maturation of the foetal brain. Clinical and preclinical findings suggest long-term consequences of SSRI perinatal exposure for the offspring. The mechanisms of SSRI effects on developing brain remain largely unknown and there are no directional approaches for prevention of the consequences of maternal SSRI treatment during pregnancy. The heptapeptide Semax (MEHFPGP) is a synthetic analogue of ACTH(4-10) which exerts marked nootropic and neuroprotective activities. The aim of the present study was to investigate the long-term effects of neonatal exposure to the SSRI fluvoxamine (FA) in white rats. Additionally, the study examined the potential for Semax to prevent the negative consequences of neonatal FA exposure. Rat pups received FA or vehicle injections on postnatal days 1-14, a time period equivalent to 27-40&#xa0;weeks of human foetal age. After FA treatment, rats were administered with Semax or vehicle on postnatal days 15-28. During the 2nd month of life, the rats underwent behavioural testing, and monoamine levels in brain structures were measured. It was shown that neonatal FA exposure leads to the impaired emotional response to stress and novelty and delayed acquisition of food-motivated maze task in adolescent and young adult rats. Furthermore, FA exposure induced alterations in the monoamine levels in brains of 1- and 2- month-old rats. Semax administration reduced the anxiety-like behaviour, improved learning abilities and normalized the levels of brain biogenic amines impaired by the FA exposure. The results demonstrate that early-life FA exposure in rat pups produces long-term disturbances in their anxiety-related behaviour, learning abilities, and brain monoamines content. Semax exerts a favourable effect on behaviour and biogenic amine system of rats exposed to the antidepressant. Thus, peptide Semax can prevent behavioural deficits caused by altered 5-HT levels during development.

Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain.

The heptapeptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is an analogue of the N-terminal fragment (4-10) of adrenocorticotropic hormone which, after intranasal application, has profound effects on learning and memory formation in rodents and humans, and also exerts marked neuroprotective effects. A clue to the molecular mechanism underlying this neurotropic action was recently given by the observation that Semax stimulates the synthesis of brain-derived neurotrophic factor (BDNF), a potent modulator of synaptic plasticity, in astrocytes cultured from rat basal forebrain. In the present study, we investigated whether Semax affects BDNF levels in rat basal forebrain upon intranasal application of the peptide. In addition, we examined whether cell membranes isolated from this brain region contained binding sites for Semax. The binding of tritium-labelled Semax was found to be time dependent, specific and reversible. Specific Semax binding required calcium ions and was characterized by a mean+/-SEM dissociation constant (KD) of 2.4+/-1.0 nm and a BMAX value of 33.5+/-7.9 fmol/mg protein. Sandwich immunoenzymatic analysis revealed that Semax applied intranasally at 50 and 250 microg/kg bodyweight resulted in a rapid increase in BDNF levels after 3 h in the basal forebrain, but not in the cerebellum. These results point to the presence of specific binding sites for Semax in the rat basal forebrain. In addition, these findings indicate that the cognitive effects exerted by Semax might be associated, at least in part, with increased BDNF protein levels in this brain region.

Semax, an ACTH(4-10) analogue with nootropic properties, activates dopaminergic and serotoninergic brain systems in rodents.

Corticotrophin (ACTH) and its analogues, particularly Semax (Met-Glu-His-Phe-Pro-Gly-Pro), demonstrate nootropic activity. Close functional and anatomical links have been established between melanocortinergic and monoaminergic brain systems. The aim of present work was to investigate the effects of Semax on neurochemical parameters of dopaminergic- and serotonergic systems in rodents. The tissue content of 5-hydroxyindoleacetic acid (5-HIAA) in the striatum was significantly increased (+25%) 2 h after Semax administration. The extracellular striatal level of 5-HIAA gradually increased up to 180% within 1-4 h after Semax (0.15 mg/kg, ip) administration. This peptide alone failed to alter the tissue and extracellular concentrations of dopamine and its metabolites. Semax injected 20 min prior D: -amphetamine dramatically enhanced the effects of the latter on the extracellular level of dopamine and on the locomotor activity of animals. Our results reveal the positive modulatory effect of Semax on the striatal serotonergic system and the ability of Semax to enhance both the striatal release of dopamine and locomotor behavior elicited by D-amphetamine.

A two-stage renal disease classification based on transfer learning with hyperparameters optimization.

Renal diseases are common health problems that affect millions of people around the world. Among these diseases, kidney stones, which affect anywhere from 1 to 15% of the global population and thus; considered one of the leading causes of chronic kidney diseases (CKD). In addition to kidney stones, renal cancer is the tenth most prevalent type of cancer, accounting for 2.5% of all cancers. Artificial intelligence (AI) in medical systems can assist radiologists and other healthcare professionals in diagnosing different renal diseases (RD) with high reliability. This study proposes an AI-based transfer learning framework to detect RD at an early stage. The framework presented on CT scans and images from microscopic histopathological examinations will help automatically and accurately classify patients with RD using convolutional neural network (CNN), pre-trained models, and an optimization algorithm on images. This study used the pre-trained CNN models VGG16, VGG19, Xception, DenseNet201, MobileNet, MobileNetV2, MobileNetV3Large, and NASNetMobile. In addition, the Sparrow search algorithm (SpaSA) is used to enhance the pre-trained model's performance using the best configuration. Two datasets were used, the first dataset are four classes: cyst, normal, stone, and tumor. In case of the latter, there are five categories within the second dataset that relate to the severity of the tumor: Grade 0, Grade 1, Grade 2, Grade 3, and Grade 4. DenseNet201 and MobileNet pre-trained models are the best for the four-classes dataset compared to others. Besides, the SGD Nesterov parameters optimizer is recommended by three models, while two models only recommend AdaGrad and AdaMax. Among the pre-trained models for the five-class dataset, DenseNet201 and Xception are the best. Experimental results prove the superiority of the proposed framework over other state-of-the-art classification models. The proposed framework records an accuracy of 99.98% (four classes) and 100% (five classes).

Synacton and individual activity of synthetic and natural corticotropins.

Short endogenous peptides represent one of the most important constituents of the mammalian body's general regulatory system. Some synthesized analogs and modified natural peptides (eg, corticotropins) also show high biological activity. Nevertheless, the mechanism of action of regulatory peptides remains unclear. To explain the effects of peptides of intermolecular processes, the hypothesis that a synactonal mechanism underlies the action of regulatory peptides, exemplified by the heptapeptide Semax, has been proposed. Thus, in the total pool of Semax metabolites, which includes the cleavage products of the parental molecule, we can distinguish the functional core, represented by the major metabolic products-peptides HFPGP and PGP. These peptides have their own binding sites with similar although differing characteristics. Together with Semax, they constitute a single complex of bioregulators acting in a certain sequence and in interaction, ie, synacton. It can be assumed that the diverse clinically significant effects of the drug Semax are determined by its synacton. Specific interactions between some tritium-labeled peptides (basic constituents of the Semax synacton) and plasma membranes of neurons have been characterized. Only a few peptides of the Semax synacton showed competitive activity for the Semax binding sites. Fragments comprising 5 amino acid residues (EHFPG and HFPGP) showed the highest competitive activity. We also characterized the processes of specific ligand-receptor interactions of some tritium-labeled corticotropins ([3 H-Pro]MEHFPGP, [3 H-Pro]HFPGP, and [3 H-Pro]PGP) by applying mathematical discriminative models (Scatchard, Hill, Bjerrum, and Lineweaver-Burk plots). So the intermolecular interactions of these peptides with plasma membranes of neuronal brain targets are probably not limited by specific binding at orthosteric sites. The effect of peptides that act in the synacton considerably extends the regulatory potential of the initial molecule.

Genes That Associated with Action of ACTH-like Peptides with Neuroprotective Potential in Rat Brain Regions with Different Degrees of Ischemic Damage.

In the treatment of ischemic stroke, an innovative approach is the use of neuroprotective compounds. Natural peptides, including adrenocorticotropic hormone (ACTH), can serve as the basis for such drugs. Previously, a significant effect of non-hormonal ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP peptides on the functions of the nervous system was shown. Also, while using RNA-Seq, we firstly revealed differentially expressed genes (DEGs) that associated with peptides in the penumbra-associated region of the frontal cortex (FC) of rats at 24 h after transient middle cerebral artery occlusion (tMCAO) model. Peptides significantly reduced profile disturbances caused by ischemia for almost two-thousand DEGs in FC related to the neurotransmitter and inflammatory response. Here, we studied how peptides affected the expression of genes in the striatum with an ischemic focus, predominantly. The same animals from which we previously acquired FC were used to collect striatum samples. Peptides generated fewer DEGs in the striatum than in the FC. Both peptides tended to normalize the profile of disturbances caused by ischemia for hundreds of DEGs, whereas 152 genes showed an even more affected profile in the striatum under ACTH(6-9)PGP action. These DEGs were associated with inflammation, predominantly. About hundred genes were overlapped between both peptides in both tissues and were associated with neuroactive ligand-receptor interaction, predominantly. Thus, genes that are associated with the ACTH-like peptide action in rat brain regions with varying levels of ischemia injury were identified. Moreover, differential spatial regulation of the ischemia process in the rat brain at the transcriptome levels was discovered under peptides with different ACTH structures. We suppose that our results may be useful for selecting more effective neuroprotective drug structures in accordance with their specific tissue/damage therapeutic impact.

Insight into Glyproline Peptides' Activity through the Modulation of the Inflammatory and Neurosignaling Genetic Response Following Cerebral Ischemia-Reperfusion.

Glyprolines are Gly-Pro (GP)- or Pro-Gly (PG)-containing biogenic peptides. These peptides can act as neutrophil chemoattractants, or atheroprotective, anticoagulant, and neuroprotective agents. The Pro-Gly-Pro (PGP) tripeptide is an active factor of resistance to the biodegradation of peptide drugs. The synthetic Semax peptide, which includes Met-Glu-His-Phe (MEHF) fragments of adrenocorticotropic hormone and the C-terminal tripeptide PGP, serves as a neuroprotective drug for the treatment of ischemic stroke. Previously, we revealed that Semax mostly prevented the disruption of the gene expression pattern 24 h after a transient middle cerebral artery occlusion (tMCAO) in a rat brain model. The genes of this pattern were grouped into an inflammatory cluster (IC) and a neurotransmitter cluster (NC). Here, using real-time RT-PCR, the effect of other PGP-containing peptides, PGP and Pro-Gly-Pro-Leu (PGPL), on the expression of a number of genes in the IC and NC was studied 24 h after tMCAO. Both the PGP and PGPL peptides showed Semax-unlike effects, predominantly without changing gene expression 24 h after tMCAO. Moreover, there were IC genes (iL1b, iL6, and Socs3) for PGP, as well as IC (iL6, Ccl3, Socs3, and Fos) and NC genes (Cplx2, Neurod6, and Ptk2b) for PGPL, that significantly changed in expression levels after peptide administration compared to Semax treatment under tMCAO conditions. Furthermore, gene enrichment analysis was carried out, and a regulatory gene network was constructed. Thus, the spectra of the common and unique effects of the PGP, PGPL, and Semax peptides under ischemia-reperfusion were distinguished.

Antidepressant-like and antistress effects of the ACTH(4-10) synthetic analogs Semax and Melanotan II on male rats in a model of chronic unpredictable stress.

Current antidepressant therapy shows substantial limitations, and there is an urgent need for the development of new treatment strategies for depression. Stressful events and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis play an important role in the pathogenesis of depression. HPA axis activity is self-regulated by negative feedback at several levels including adrenocorticotropic hormone (ACTH)-mediated feedback. Here, we investigated whether noncorticotropic synthetic analogs of the ACTH(4-10) fragment, ACTH(4-7)-Pro-Gly-Pro (Semax) and Ac-Nle4-cyclo[Asp5-His6-D-Phe7-Arg8-Trp9-Lys10]ACTH(4-10)-NH2 (Melanotan II (MTII), a potent agonist of melanocortin receptors), have potential antidepressant activity in a chronic unpredictable stress (CUS) rat model of depression. Stressed and control male adult Sprague-Dawley rats received daily intraperitoneal injections of saline or a low dose (60&#xa0;nmol/kg of body weight (BW)) of Semax or MTII. Rats were monitored for BW and hedonic status, as measured in the sucrose preference test. We found that chronic treatment with Semax and MTII reversed or substantially attenuated CUS-induced anhedonia, BW gain suppression, adrenal hypertrophy and a decrease in the hippocampal levels of BDNF. In the forced swim test, no effects of the CUS procedure or peptides on the duration of rat immobility were detected. Our findings show that in the CUS paradigm, systemically administered ACTH(4-10) analogs Semax and MTII exert antidepressant-like effects on anhedonia and hippocampal BDNF levels, and attenuate markers of chronic stress load, at least in male rats. The results support the argument that ACTH(4-10) analogs and other noncorticotropic melanocortins may have promising therapeutic potential for the treatment and prevention of depression and other stress-related pathologies.

SkinNet-16: A deep learning approach to identify benign and malignant skin lesions.

Skin cancer these days have become quite a common occurrence especially in certain geographic areas such as Oceania. Early detection of such cancer with high accuracy is of utmost importance, and studies have shown that deep learning- based intelligent approaches to address this concern have been fruitful. In this research, we present a novel deep learning- based classifier that has shown promise in classifying this type of cancer on a relevant preprocessed dataset having important features pre-identified through an effective feature extraction method. Skin cancer in modern times has become one of the most ubiquitous types of cancer. Accurate identification of cancerous skin lesions is of vital importance in treating this malady. In this research, we employed a deep learning approach to identify benign and malignant skin lesions. The initial dataset was obtained from Kaggle before several preprocessing steps for hair and background removal, image enhancement, selection of the region of interest (ROI), region-based segmentation, morphological gradient, and feature extraction were performed, resulting in histopathological images data with 20 input features based on geometrical and textural features. A principle component analysis (PCA)-based feature extraction technique was put into action to reduce the dimensionality to 10 input features. Subsequently, we applied our deep learning classifier, SkinNet-16, to detect the cancerous lesion accurately at a very early stage. The highest accuracy was obtained with the Adamax optimizer with a learning rate of 0.006 from the neural network-based model developed in this study. The model also delivered an impressive accuracy of approximately 99.19%.

Optimizing home energy management: Robust and efficient solutions powered by attention networks.

This paper explores the integration of attention networks in the realm of home energy management systems (HEMS) to enhance the robustness and efficiency of energy consumption optimization. With the growing demand for smart grid technologies, the need to achieve demand side response becomes paramount. The proposed solution leverages attention networks to dynamically allocate significance to various aspects of energy consumption patterns, considering the diverse load types and dynamic loading scenarios present in households. In this investigation, we focus on the AMpds2 dataset, characterized by intricate loading patterns, and assess its performance across various time series forecasting methodologies, including (RNN), (LSTM), (TCN), and transformers. Multiple methodologies undergo performance evaluation using diverse hyperparameter combinations. Evaluation metrics, specifically (RMSE) and (MAE), are employed. Advanced optimizers such as (Adam) and (Adamax) are applied, and activation functions, including sigmoid, linear, tanh, and ReLU, are implemented. A comprehensive performance analysis involves 16 hyperparameter combinations across four distinct time series models. Through meticulous scrutiny, it is determined that the utilization of transformers in forecasting energy and load patterns results in a 4% increase in accuracy, as elucidated in the results section. The implementation of this study is carried out on the Python 3.2 platform, and the matplotlib library is employed to visualize the comparison between actual and predicted data.

[Nootropic and analgesic effects of Semax following different routes of administration].

Heptapeptide Semax (MEHFPGP) is the fragment of ACTH(4-10) analogue with prolonged neurotropic activity. The aim of the present work was to study the Semax effects on learning capability and pain sensitivity in white rats following intraperitoneal and intranasal administration in different doses. Semax nootropic effects were studied in the test of acquisition of passive avoidance task. Pain sensitivity was estimated in Randall-Selitto paw-withdrawal test. It was shown that Semax exerts nootropic and analgesic activities following intraperitoneal administration. Analysis of dependence of these effects on dose resulted in different dose-response curves. Following intranasal administration, Semax was more potent in learning improvement compared to intraperitoneal administration. The peptide failed to affect the animal pain sensitivity following intranasal administration as opposed to intraperitoneal administration. The data obtained suggest different mechanisms and brain structures involved in realization of the nootropic and analgesic effects of Semax.

Novel Insights into the Protective Properties of ACTH(4-7)PGP (Semax) Peptide at the Transcriptome Level Following Cerebral Ischaemia-Reperfusion in Rats.

Cerebral ischaemia is the most common cause of impaired brain function. Biologically active peptides represent potential drugs for reducing the damage that occurs after ischaemia. The synthetic melanocortin derivative, ACTH(4-7)PGP (Semax), has been used successfully in the treatment of patients with severe impairment of cerebral blood circulation. However, its molecular mechanisms of action within the brain are not yet fully understood. Previously, we used the transient middle cerebral artery occlusion (tMCAO) model to study the damaging effects of ischaemia-reperfusion on the brain transcriptome in rats. Here, using RNA-Seq analysis, we investigated the protective properties of the Semax peptide at the transcriptome level under tMCAO conditions. We have identified 394 differentially expressed genes (DEGs) (>1.5-fold change) in the brains of rats at 24 h after tMCAO treated with Semax relative to saline. Following tMCAO, we found that Semax suppressed the expression of genes related to inflammatory processes and activated the expression of genes related to neurotransmission. In contrast, ischaemia-reperfusion alone activated the expression of inflammation-related genes and suppressed the expression of neurotransmission-related genes. Therefore, the neuroprotective action of Semax may be associated with a compensation of mRNA expression patterns that are disrupted during ischaemia-reperfusion conditions.

[A comparative chemoreactome analysis of mexidol].

To compare mexidol with control molecules (choline alfoscerate, piracetam, glycine, semax) using chemoreactome analysis. The chemical structure of mexidol was compared to molecule metabolites extracted from the Human Metabolome Database (HMDB) and a drug database. More than 40 000 of metabolites from HMDB were used as a model of human metabolome. The chemoreactome analysis showed that mexidol may be (1) an agonist of acetylcholine and GABA-A receptors; (2) an anti-inflammatory agent, the effects of which are carried out by inhibiting the synthesis of pro-inflammatory prostaglandins; (3) a neurotrophic agent with neuroprotective properties; (4) a coagulation inhibitor; (5) a diabetes medication and (6) a hypolipidemic agent. Compared to 'control' molecules, mexidol has a more pronounced safety profile (a lower impact on serotonin, dopamine and adrenergic receptors, a lesser degree of interaction with the potassium channels of the heart, MAO and P450 cytochromes). The results of modeling allow to specify the mechanisms of action of mexidol at the molecular level.

An intelligent LinkNet-34 model with EfficientNetB7 encoder for semantic segmentation of brain tumor.

A brain tumor is an unnatural expansion of brain cells that can't be stopped, making it one of the deadliest diseases of the nervous system. The brain tumor segmentation for its earlier diagnosis is a difficult task in the field of medical image analysis. Earlier, segmenting brain tumors was done manually by radiologists but that requires a lot of time and effort. Inspite of this, in the manual segmentation there was possibility of making mistakes due to human intervention. It has been proved that deep learning models can outperform human experts for the diagnosis of brain tumor in MRI images. These algorithms employ a huge number of MRI scans to learn the difficult patterns of brain tumors to segment them automatically and accurately. Here, an encoder-decoder based architecture with deep convolutional neural network is proposed for semantic segmentation of brain tumor in MRI images. The proposed method focuses on the image downsampling in the encoder part. For this, an intelligent LinkNet-34 model with EfficientNetB7 encoder based semantic segmentation model is proposed. The performance of LinkNet-34 model is compared with other three models namely FPN, U-Net, and PSPNet. Further, the performance of EfficientNetB7 used as encoder in LinkNet-34 model has been compared with three encoders namely ResNet34, MobileNet_V2, and ResNet50. After that, the proposed model is optimized using three different optimizers such as RMSProp, Adamax and Adam. The LinkNet-34 model has outperformed with EfficientNetB7 encoder using Adamax optimizer with the value of jaccard index as 0.89 and dice coefficient as 0.915.

Stability of Semax acetyl to proteolysis in various biological media.

Therapeutic possibility of "Semax" for depression.

Brain Protein Expression Profile Confirms the Protective Effect of the ACTH(4-7)PGP Peptide (Semax) in a Rat Model of Cerebral Ischemia-Reperfusion.

The Semax (Met-Glu-His-Phe-Pro-Gly-Pro) peptide is a synthetic melanocortin derivative that is used in the treatment of ischemic stroke. Previously, studies of the molecular mechanisms underlying the actions of Semax using models of cerebral ischemia in rats showed that the peptide enhanced the transcription of neurotrophins and their receptors and modulated the expression of genes involved in the immune response. A genome-wide RNA-Seq analysis revealed that, in the rat transient middle cerebral artery occlusion (tMCAO) model, Semax suppressed the expression of inflammatory genes and activated the expression of neurotransmitter genes. Here, we aimed to evaluate the effect of Semax in this model via the brain expression profiling of key proteins involved in inflammation and cell death processes (MMP-9, c-Fos, and JNK), as well as neuroprotection and recovery (CREB) in stroke. At 24 h after tMCAO, we observed the upregulation of active CREB in subcortical structures, including the focus of the ischemic damage; downregulation of MMP-9 and c-Fos in the adjacent frontoparietal cortex; and downregulation of active JNK in both tissues under the action of Semax. Moreover, a regulatory network was constructed. In conclusion, the suppression of inflammatory and cell death processes and the activation of recovery may contribute to the neuroprotective action of Semax at both the transcriptome and protein levels.

Semax, an analog of ACTH(4-7), regulates expression of immune response genes during ischemic brain injury in rats.

Brain stroke continues to claim the lives of million people every year. To build the effective strategies for stroke treatment it is necessary to understand the neuroprotective mechanisms that are able to prevent the ischemic injury. Consisting of the ACTH(4-7) fragment and the tripeptide Pro-Gly-Pro (PGP), the synthetic peptide Semax effectively protects brain against ischemic stroke. However, the molecular mechanisms underlying its neuroprotection and participation of PGP in them are still needed to be clarified. To reveal biological processes and signaling pathways, which are affected by Semax and PGP, we performed the transcriptome analysis of cerebral cortex of rats with focal cerebral ischemia treated by these peptides. The genome-wide biochip data analysis detected the differentially expressed genes (DEGs) and bioinformatic web-tool Ingenuity iReport found DEGs associations with several biological processes and signaling pathways. The immune response is the process most markedly affected by the peptide: Semax enhances antigen presentation signaling pathway, intensifies the effect of ischemia on the interferon signaling pathways and affects the processes for synthesizing immunoglobulins. Semax significantly increased expression of the gene encoding the immunoglobulin heavy chain, highly affects on cytokine, stress response and ribosomal protein-encoding genes after occlusion. PGP treatment of rats with ischemia attenuates the immune activity and suppresses neurotransmission in the CNS. We suppose that neuroprotective mechanism of Semax is realized via the neuroimmune crosstalk, and the new properties of PGP were found under ischemia. Our results provided the basis for further proteomic investigations in the field of searching Semax neuroprotection mechanism.

Gateways to clinical trials.

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 3-AP, Adalimumab, adefovir dipivoxil, AeroDose albuterol inhaler, agalsidase alfa, alemtuzumab, aminolevulinic acid methyl ester, anidulafungin, anthrax vaccine, anti-CTLA-4 MAb, azimilide hydrochloride; Bevacizumab, BG-12, bimatoprost, bortezomib, bosentan, botulinum toxin type B; Caspofungin acetate, ceftobiprole, certolizumab pegol, CG-53135, cilansetron; Darbepoetin alfa, degarelix acetate, dimethylfumarate, duloxetine hydrochloride, dutasteride; Eicosapentaenoic acid/docosahexaenoic acid, eletriptan, entecavir, esomeprazole magnesium, exatecan mesilate, exenatide, ezetimibe; Falecalcitriol, fampridine, fondaparinux sodium, fontolizumab; Gefitinib, gepirone hydrochloride; Human insulin; IDEA-070, imatinib mesylate, iodine (I131) tositumomab; Lanthanum carbonate, lubiprostone; Mafosfamide cyclohexylamine salt, melatonin; NC-531, nemifitide ditriflutate, neridronic acid, nolatrexed dihydrochloride; Oral insulin; Palifermin, parecoxib sodium, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, plerixafor hydrochloride, posaconazole, pramlintide acetate, pregabalin, PT-141; Quercetin; Ranibizumab, renzapride hydrochloride, RSD-1235; Sabarubicin hydrochloride, semapimod hydrochloride, Semax, SHL-749; Tegaserod maleate, tenatoprazole, tetrodotoxin, tolevamer sodium, trabectedin, travoprost, travoprost/timolol; Valdecoxib, visilizumab, Xcellerated T cells, XP-828L; Zoledronic acid monohydrate.