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Neurological disorders have become severe and dreadful issues around the globe that are rarely directly mediated because of the blood-brain barrier (BBB). Despite the various therapeutic strategies, including the utilization of cholinesterase inhibitors, metal chelators, molecular chaperones, and anti-body treatment that have been put forth, drug delivery to the brain has remained a problem in the treatment of neurodegenerative disorders (NDD). Chitosan, one of nature's multifunctional polymers, is acknowledged as a useful chemical in the medical and pharmaceutical industries due to its distinctive and flexible biological characteristics. By using Chitosan and its derivatives as drug delivery methods, it is possible to give medications in a sustained and regulated way, increase their stability, and lessen the likelihood of adverse drug reactions. In the current review, we have concentrated on the significance of Chitosan and its derivatives to become a hotspot in drug delivery, particularly for NDDs. This review also explains their properties as drug delivery vectors and their ability to cross the BBB, which is a significant obstacle to medication administration in NDDs. In conclusion, this review suggests that expanding the scope of such research would make it possible to develop NDD drug delivery systems that are more efficient.

Abstract Leber’s hereditary optic neuropathy (LHON) is a mitochondrial hereditary disease in which visual loss affects complex 1 activity of the electron transport chain of mitochondria. It first manifests as painless dulling or blurry in one or even both eyes, and as it develops, sharpness and color perception are lost. In addition to primary mitochondrial DNA (mtDNA) mutations, there are also other environmental and epigenetic factors involved in the pathogenesis of LHON. One of the most common locations for deadly pathogenic mutations in humans is the human complex I accessory NDUFS4 subunit gene. The iron-sulfur clusters of the electron input domain were distorted in the absence of NDUFS4, which reduced complex I function and elevated the production of reactive oxygen species. Therefore, here, we studied the epigenetic alterations of NDUFS4 by focusing on histone activation and repressive markers. We isolated peripheral blood mononuclear cells (PBMCs) from LHON patients and healthy individuals and examined epigenetic modifications in ND4 mutant cells and control cells. Chromatin immunoprecipitation-qRT PCR (ChIP-qRT PCR) assays were performed to investigate the modifications of histones. In comparison to their controls, both LHON patients and ND4 mutant cells exhibited a significant enrichment in activation and repressive markers. This finding indicates that these modifications might mitigate the impact of LHON mutations on complex 1 and aid in elucidating the mechanism underlying the progression of LHON disease.

With the current global population expansion and increasing life expectancy, more people are living in their later years, when neurological issues are most common. Both environmental and geographical factors contribute to the incidence of various neurological diseases (NDs) in India. These diseases involve the gradual or complete loss of structure and function of neurons, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), epilepsy, stroke, and amyotrophic lateral sclerosis (ALS). The exact cause of these illnesses is still unknown in medicine. Still, it may be linked to protein deterioration, oxidative stress, inflammation, environmental factors, mitochondrial deficiencies, familial history, and abnormal protein build-up. In this review, we have discussed briefly the pathophysiology of various neurological diseases from Indian studies as well as possible diagnostic markers, drugs used, traditional Indian medicinal plants, and alternative therapeutic approaches for detecting and treating these NDs.

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Respiratory tract infections remain the leading cause of morbidity and mortality worldwide. The burden is further increased by polymicrobial infection or viral and bacterial co-infection, often exacerbating the existing condition. Way back in 1918, high morbidity due to secondary pneumonia caused by bacterial infection was known, and a similar phenomenon was observed during the recent COVID-19 pandemic in which secondary bacterial infection worsens the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) condition. It has been observed that viruses paved the way for subsequent bacterial infection; similarly, bacteria have also been found to aid in viral infection. Viruses elevate bacterial infection by impairing the host’s immune response, disrupting epithelial barrier integrity, expression of surface receptors and adhesion proteins, direct binding of virus to bacteria, altering nutritional immunity, and effecting the bacterial biofilm. Similarly, the bacteria enhance viral infection by altering the host’s immune response, up-regulation of adhesion proteins, and activation of viral proteins. During co-infection, respiratory bacterial and viral pathogens were found to adapt and co-exist in the airways of their survival and to benefit from each other, i.e., there is a cooperative existence between the two. This review comprehensively reviews the mechanisms involved in the synergistic/cooperativity relationship between viruses and bacteria and their interaction in clinically relevant respiratory infections.

Heavy metals (HMs) are metallic substances. They enter biotic and abiotic systems through natural and human activities. These HMs have an impact on the atmosphere, soil, and groundwater, and they also affect all living things, especially humans, when they enter the food chain. Therefore, monitoring and removing HMs from the environment and humans are crucial for maintaining HMs-based toxicity. The detection of HMs from environmental and human samples has been performed by techniques such as atomic adsorption spectrometry (AAS) and inductively coupled plasma mass spectrometry (ICP-MS). With the advancement of AI-based technology, HMs are now detected and removed from the environment and human systems. This review discusses the impact of HMs on the environment and human health, their detection and removal techniques, and the integration of recent advancements in AI-based technology for the detection and removal of HMs from environmental and human samples.

Several proteins and peptides have therapeutic potential and can be used for cancer therapy. By binding to cell surface receptors and other indicators uniquely linked with or overexpressed on tumors compared to healthy tissue, protein biologics enhance the active targeting of cancer cells, as opposed to the passive targeting of cells by conventional small-molecule chemotherapeutics. This study focuses on peptide medications that exist to slow or stop tumor growth and the spread of cancer, demonstrating the therapeutic potential of peptides in cancer treatment. As an alternative to standard chemotherapy, peptides that selectively kill cancer cells while sparing healthy tissue are developing. A mountain of clinical evidence supports the efficacy of peptide-based cancer vaccines. Since a single treatment technique may not be sufficient to produce favourable results in the fight against cancer, combination therapy is emerging as an effective option to generate synergistic benefits. One example of this new area is the use of anticancer peptides in combination with nonpeptidic cytotoxic drugs or the combination of immunotherapy with conventional therapies like radiation and chemotherapy. This review focuses on the different natural and synthetic peptides obtained and researched. Discoveries, manufacture, and modifications of peptide drugs, as well as their contemporary applications, are summarized in this review. We also discuss the benefits and difficulties of potential advances in therapeutic peptides.

Peptides, short protein fragments, can emulate the functions of their full-length native counterparts. Peptides are considered potent recombinant protein alternatives due to their specificity, high stability, low production cost, and ability to be easily tailored and immobilized. Stem cell proliferation and differentiation processes are orchestrated by an intricate interaction between numerous growth factors and proteins and their target receptors and ligands. Various growth factors, functional proteins, and cellular matrix-derived peptides efficiently enhance stem cell adhesion, proliferation, and directed differentiation. For that, peptides can be immobilized on a culture plate or conjugated to scaffolds, such as hydrogels or synthetic matrices. In this review, we assess the applications of a variety of peptides in stem cell adhesion, culture, organoid assembly, proliferation, and differentiation, describing the shortcomings of recombinant proteins and their full-length counterparts. Furthermore, we discuss the challenges of peptide applications in stem cell culture and materials design, as well as provide a brief outlook on future directions to advance peptide applications in boosting stem cell quality and scalability for clinical applications in tissue regeneration.

Ocular cells like, retinal pigment epithelium (RPE) is a highly specialized pigmented monolayer of post-mitotic cells, which is located in the posterior segment of the eye between neuro sensory retina and vascular choroid. It functions as a selective barrier and nourishes retinal visual cells. As a result of high-level oxygen consumption of retinal cells, RPE cells are vulnerable to chronic oxidative stress and an increased level of reactive oxygen species (ROS) generated from mitochondria. These oxidative stress and ROS generation in retinal cells lead to RPE degeneration. Various sources including mtDNA damage could be an important factor of oxidative stress in RPE. Gene therapy and mitochondrial transfer studies are emerging fields in ocular disease research. For retinal degenerative diseases stem cell-based transplantation methods are developed from basic research to preclinical and clinical trials. Translational research contributions of gene and cell therapy would be a new strategy to prevent, treat and cure various ocular diseases. This review focuses on the effect of oxidative stress in ocular cell degeneration and recent translational researches on retinal degenerative diseases to cure blindness.

Abstract Background Drugs are chemicals which can disrupt the nerve cell functions of the brain. The present study aims to investigate the addiction related gene (OPRM1) in three types of addiction—drugs, alcohol and smoking. Pathway for the addiction was ascertained through KEGG database, and the hotspot mutations for various populations were identified from Gnomad-exomes database. In silico analyses like SIFT, Polyphen, Hope, I-mutant and mutation taster were performed to understand the amino acid substitution, protein function, stability and pathogenicity of the variants. Main body Addiction-related variants were found in exons 1, 2 and 3, while the exon 4 did not exhibit any addiction related variation. Among all the variants from this gene, rs1799971 (A118G) polymorphism was the most commonly studied variation for addiction in different populations worldwide. Population-wise allele and genotype frequencies, demographic and epidemiological studies have also been performed from different populations, and the possible association of these variants with addiction was evaluated. Conclusion Our findings suggest that OPRM1 polymorphism impact as pharmacogenetic predictor of response to naltrexone and can also address the genetic predisposition related to addiction in human beings.

Placental complication arises due to various risk factors occurring during the pregnancy period, leading to an increased morbidity rate. Placenta related disorders are one of primary reason for pregnancy related complications and the clinical incidences are seen to be on the rise. Most of the common disorders associated with placenta are pre-eclampsia, recurrent spontaneous abortions, intra-uterine growth restriction etc. Several studies have been done to understand the genetics and immunological attributes leading to the development of placenta associated complications. In the recent years, studies were able to establish and identify ncRNAs found specifically in foetal tissues such as the placenta. The aberrant expression patterns of ncRNA associated with placenta has been linked to disorders such as pre-eclampsia. Since ncRNA play a major role in regulating biological processes like trophoblast growth, migration and invasion, their aberrant expression could very well lead to complications like spontaneous pregnancy loss. This review article focuses on the association of ncRNAs - miRNAs, lncRNAs, CircRNAs in placenta associated complications as well as the different ncRNA based therapies. Deciphering the exact mechanism involved in the regulation and development of placenta through ncRNA will help in using it as a biomarker for early diagnosis. Understanding the therapeutic opportunities of ncRNAs in placental disorders will result in better treatment strategies.

Neuro-oncological diseases are rare and their fatality rate is increased in patients due to advance disease development despite of the recent outcomes on neuro-oncological therapies. Artificial intelligence (AI) approaches and the exponential expansion of computing algorithms are set to increase the precision of diagnostic and therapeutic approaches in medicine. Medical imaging is one of the common AI applications where it assists radiologists in diagnosis. Radiomics has been successfully applied in neuro-oncology and it will be at forefront of AI revolution. Various AI methods can define numerous infiltrating margins of neuro-oncological diseases and it differentiates pseudo-progression from real progression and envisage recurrence and survival better than the methods used in routine practice. The present review deliberates the common neuro-oncological diseases such as glioblastoma, meningioma, spinal cord tumor and neurofibroma (NF1) and its AI algorithms related to imaging techniques such as computed (MRI) and computed tomography (CT). Also, we have discussed the beneficial aspect of AI and recent trends in diagnosis. From the study, the management of neuro-oncological diseases using AI can be revolutionized and the need of omics analysis is essential in future.

According to the Centers for Disease Control and Prevention (CDC), more than 700,000 women have been diagnosed with cancer in the last five years. Cancers of the breast, cervical, ovarian, lung, uterine, and thyroid are among the most prevalent cancers in women. For over a century, surgery, radiation, and pharmaceutical treatment have been the cornerstones of cancer treatment. When used alone or in combination, these medicines have improved therapeutic outcomes for patients with a variety of solid and diffuse malignancies, but there is still a significant unmet demand for improved survival and quality of life. As seen by the advancement from first laboratory observations to the completion of multiple clinical trials, electrical-based cancer therapies have made remarkable progress as a potential therapeutic agent for the treatment of many solid tumours. Electric field lines have the opportunity to utilize force on charged molecules, which distinguishes them. By interacting with polar molecules like tubulin and disrupting the mitotic spindle, electric fields can potentially have an antimitotic effect on cells, reducing or stopping cell proliferation. In a range of tumour types, Tumor Treating Fields (TTFields) have been found to have anti-mitotic effects. The combined effect of TTFields and paclitaxel increased apoptosis-mediated anti-mitotic tumour progression inhibition. In conclusion, this study provides an overview of the most common female cancers as well as an up-to-date assessment of the therapy options for these diseases. It also covers the use of electric module therapy for certain tumours, its putative mechanisms, and a synthesis of its benefits and drawbacks during cancer treatment.

Cervical cancer (CC) caused by human papillomavirus (HPV) is one of the largest causes of malignancies in women worldwide. Cisplatin is one of the widely used drugs for the treatment of CC is rendered ineffective owing to drug resistance. This review highlights the cause of resistance and the mechanism of cisplatin resistance cells in CC to develop therapeutic ventures and strategies that could be utilized to overcome the aforementioned issue. These strategies would include the application of nanocarries, miRNA, CRIPSR/Cas system, and chemotherapeutics in synergy with cisplatin to not only overcome the issues of drug resistance but also enhance its anti-cancer efficiency. Moreover, we have also discussed the signaling network of cisplatin resistance cells in CC that would provide insights to develop therapeutic target sites and inhibitors. Furthermore, we have discussed the role of CC metabolism on cisplatin resistance cells and the physical and biological factors affecting the tumor microenvironments.

Parkinson’s disease (PD) is a neurodegenerative disorder which mainly targets motor symptoms such as tremor, rigidity, bradykinesia and postural instability. The physiological changes occur due to dopamine depletion in basal ganglia region of the brain. PD aetiology is not yet elucidated clearly but genetic and environmental factors play a prominent role in disease occurrence. Despite of various environmental factors, pesticides exposure has been convicted as major candidate in PD pathogenesis. Among various pesticides 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been widely investigated in PD following with paraquat (PQ), maneb (MB), organochlorines (OC) and rotenone. Effect of these pesticides has been suggested to be involved in oxidative stress, alterations in dopamine transporters, mitochondrial dysfunction, α-synuclein (αSyn) fibrillation, and neuroinflammation in PD. The present review discusses the influence of pesticides in neurodegeneration and its related epidemiological studies conducted in PD. Furthermore, we have deliberated the common pesticides involved in PD and its associated genetic alterations and the probable mechanism of them behind PD pathogenesis. Hence, we conclude that pesticides play a prominent role in PD pathogenesis and advance research is needed to investigate the alterations in genetic and mechanistic aspects of PD.

Objectives: Cell entry of SARS-CoV-2 depends on angiotensin-converting enzyme II. Angiotensin-converting enzyme II is homologous with, but acts antagonistically to, angiotensin-converting enzyme and has the critical function of protecting the lungs. Angiotensin-converting enzyme inhibitors are major antihypertensive agents. Thus, we aimed to analyze the impact of the prevalence of preexisting hypertension on the local spread of COVID-19. Methods: Data on SARS-CoV-2 infection and the estimated number of patients who received medical treatment on the basis of disease classification using the International Statistical Classification of Diseases and Related Health Problems (10th Revision) in each prefecture were obtained from the official Japanese notifications database. We analyzed the association between the proportion of patients with each disease and SARS-CoV-2-infection prevalence. Results: The ratio of patients treated for diseases of the circulatory system, especially hypertensive disorders, per population demonstrated the most significant negative correlation with SARS-CoV-2-infection prevalence (Spearman’s rank correlation, P < 0.01). Age group analysis revealed a significant negative correlation in age groups 35–44, 45–54, 55–64, 75–84, and ≥85. Conclusions: Our findings suggest that hypertension treatment may play a protective role against the local spread of SARS-CoV-2 infection.

Heavy metal Chromium (Cr), can adversely affect humans and their health if accumulated in organs of the body, such as the lungs, liver, and kidneys. Cr (VI) is highly toxic and has a higher solubility in water than Cr (III). One of the most common routes for Cr exposure is through inhalation and is associated with liver, lung, kidney damage, widespread dermatitis, GI tract damage, human lung cancer, cardiomyopathies, and cardiovascular disease. The increase in ROS production has been attributed to most of the damage caused by Cr toxicity. Cr-induced ROS-mediated oxidative stress has been seen to cause a redox imbalance affecting the antioxidant system balance in the body. The Nrf2 pathway dysregulation has been implicated in the same. Deregulation of histone acetylation and methylation has been observed, together with gene methylation in genes such as p16, MGMT, APC, hMLH1, and also miR-143 repression. Several ultra-structural changes have been observed following Cr (VI)-toxicity, including rough ER dilation, alteration in the mitochondrial membrane and nuclear membrane, pycnotic nuclei formation, and cytoplasm vacuolization. A significant change was observed in the metabolism of lipid, glucose, and the metabolism of protein after exposure to Cr. Cr-toxicity also leads to immune system dysregulations with changes seen in the expression of IL-8, IL-4, IgM, lymphocytes, and leukocytes among others. P53, as well as pro-and anti-apoptotic proteins, are involved in apoptosis. These Cr-induced damages can be alleviated via agents that restore antioxidant balance, regulate Nrf-2 levels, or increase anti-apoptotic proteins while decreasing pro-apoptotic proteins.

Infection with viruses, bacteria, and parasites are thought to be the underlying cause of about 8–17% of the world’s cancer burden, i.e., approximately one in every five malignancies globally is caused by an infectious pathogen. Oncogenesis is thought to be aided by eleven major pathogens. It is crucial to identify microorganisms that potentially act as human carcinogens and to understand how exposure to such pathogens occur as well as the following carcinogenic pathways they induce. Gaining knowledge in this field will give important suggestions for effective pathogen-driven cancer care, control, and, ultimately, prevention. This review will mainly focus on the major onco-pathogens and the types of cancer caused by them. It will also discuss the major pathways which, when altered, lead to the progression of these cancers.

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Toxic heavy metals (THMs) are non-essential hazardous environmental pollutants with intractable health challenges in humans and animals. Exposure to lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), nickel (Ni), and chromium (Cr) are ubiquitous and unavoidable due to food contamination, mining, and industrial mobilization. They are triggers of tissue impairment and aberrant signaling pathways that cascade into several toxicities and pathologies. Each of Pb, Cd, Hg, As, Ni, and Cr aggravate oxidative inflammation, protein dysregulation, apoptotic induction, DNA damage, endocrine deficits, and mitochondrial dysfunction contributing to the pathophysiology of diseases. Hesperidin (HSD) and hesperetin (HST) are flavonoids from citrus fruits, and systematic investigations suggest their potential to combat the molecular alterations and toxicities induced by THMs. They mitigate heavy metal toxicity via antioxidant, anti-inflammatory, and anti-apoptotic effects via scavenging free radicals and modulation of ATPases, cell cycle proteins, and various cellular signaling pathways, including Nrf2/HO-1/ARE, PI3K/mTOR/Akt, MAPK/caspase-3/Bax/Bcl-2, iNOS/NF-κB/TNF-α/COX-2. This review summarized the mechanistic effects of heavy metal toxicity and the insights on molecular mechanisms underlying mitigation of heavy metal toxicity by HSD and HST. Hesperidin and hesperetin are potential flavonoids for the modulation of pathological signaling networks associated with THMs. Therefore, HSD and HST can be suggested as natural dietary agents and blockers of harmful effects of THMs.

Abstract Background The lack of early diagnostic tools and the development of chemoresistance have made ovarian cancer (OC) one of the deadliest gynaecological cancers. The tumour microenvironment is characterised by the extracellular release of high levels of ATP, which is followed by the activation of P1 adenosinergic and P2 purinergic signalling systems. The sequential hydrolysis of ATP by the ectonucleotidases CD39 and CD73 generates adenosine, which creates an immune suppressive microenvironment by inhibiting the T and NK cell responses via the A2A adenosine receptor. Main body of the abstract In OC, adenosine-induced pAMPK pathway leads to the inhibition of cell growth and proliferation, which offers new treatment options to prevent or overcome chemoresistance. The activation of P2Y12 and P2Y1 purinergic receptors expressed in the platelets promotes epithelial-mesenchymal transition (EMT). The inhibitors of these receptors will be the effective therapeutic targets in managing OC. Furthermore, research on these signalling systems indicates an expanding field of opportunities to specifically target the purinergic receptors for the treatment of OC. Short conclusion In this review, we have described the complex purinergic signalling mechanism involved in the development of OC and discussed the merits of targeting the components involved in the purinergic signalling pathway.

COVID-19 has become a significant public health concern that has catastrophic consequences for society. Some preliminary evidence suggests that the male reproductive system may be an infection target for SARS-CoV-2. SARS-CoV-2 may be transmitted sexually, according to preliminary research. Testicular cells exhibit a high level of the angiotensin-converting enzyme 2 (ACE2) receptor, which enhances the entry of the SARS-CoV-2 into host cells. Some instances of COVID-19 have been documented to exhibit hypogonadism during the acute stage. Furthermore, systemic inflammatory reactions triggered by SARS-CoV-2 infection may cause oxidative stress (OS), which has been shown to have profoundly deleterious consequences on testicular functioning. This work gives a clear picture of how COVID-19 may affect male reproductive systems and calls attention to the many unanswered questions about the mechanisms by which this virus can be linked to men’s health and fertility.

Lung cancer (LC) is considered as one of the leading causes of cancer-associated mortalities. Cancer cells’ reprogrammed metabolism results in changes in metabolite concentrations, which can be utilized to identify a distinct metabolic pattern or fingerprint for cancer detection or diagnosis. By detecting different metabolic variations in the expression levels of LC patients, this will help and enhance early diagnosis methods as well as new treatment strategies. The majority of patients are identified at advanced stages after undergoing a number of surgical procedures or diagnostic testing, including the invasive procedures. This could be overcome by understanding the mechanism and function of differently regulated metabolites. Significant variations in the metabolites present in the different samples can be analyzed and used as early biomarkers. They could also be used to analyze the specific progression and type as well as stages of cancer type making it easier for the treatment process. The main aim of this review article is to focus on rewired metabolic pathways and the associated metabolite alterations that can be used as diagnostic and therapeutic targets in lung cancer diagnosis as well as treatment strategies.

Prostate cancer (PCa) is the common cause of death in men. The pathophysiological factors contributing to PCa are not well known. PCa cells gain a protective mechanism via abnormal lipid signaling and metabolism. PCa cells modify their metabolism in response to an excessive intake of nutrients to facilitate advancement. Metabolic syndrome (MetS) is inextricably linked to the carcinogenic progression of PCa, which heightens the severity of the disease. It is hypothesized that changes in the metabolism of the mitochondria contribute to the onset of PCa. The studies of particular alterations in the progress of PCa are best accomplished by examining the metabolome of prostate tissue. Due to the inconsistent findings written initially, additional epidemiological research is required to identify whether or not MetS is an aspect of PCa. There is a correlation between several risk factors and the progression of PCa, one of which is MetS. The metabolic symbiosis between PCa cells and the tumor milieu and how this type of crosstalk may aid in the development of PCa is portrayed in this work. This review focuses on in-depth analysis and evaluation of the metabolic changes that occur within PCa, and also aims to assess the effect of metabolic abnormalities on the aggressiveness status and metabolism of PCa.

As a complex endocrine and metabolic condition, polycystic ovarian syndrome (PCOS) affects women’s reproductive health. These common symptoms include hirsutism, hyperandrogenism, ovulatory dysfunction, irregular menstruation, and infertility. No one knows what causes it or how to stop it yet. Alterations in gut microbiota composition and disruptions in secondary bile acid production appear to play a causative role in developing PCOS. PCOS pathophysiology and phenotypes are tightly related to both enteric and vaginal bacteria. Patients with PCOS exhibit changed microbiome compositions and decreased microbial diversity. Intestinal microorganisms also alter PCOS patient phenotypes by upregulating or downregulating hormone release, gut-brain mediators, and metabolite synthesis. The human body’s gut microbiota, also known as the “second genome,” can interact with the environment to improve metabolic and immunological function. Inflammation is connected to PCOS and may be caused by dysbiosis in the gut microbiome. This review sheds light on the recently discovered connections between gut microbiota and insulin resistance (IR) and the potential mechanisms of PCOS. This study also describes metabolomic studies to obtain a clear view of PCOS and ways to tackle it.

Artificial intelligence (AI) based on deep learning (DL) has sparked tremendous global interest in recent years. Deep Learning has been widely adopted in speech and image recognition, natural language processing which has an impact on healthcare. In the recent decade, the application of DL has exponentially grown in the field of Ophthalmology. The fundoscopy, slit lamp photography, optical coherence tomography (OCT), and magnetic resonance imaging (MRI) were employed for clinical examination of various ocular conditions. These data served as a perfect platform for the development of DL models in Ophthalmology. Currently, the application of DL in ocular disorders is majorly studied in Diabetic retinopathy (DR), age-related macular degeneration (AMD), macular oedema, retinopathy of prematurity (ROP), glaucoma, and cataract. In Ophthalmology, DL models are gradually expanding their scope in optic neuropathies. Glaucoma and optic neuritis are optic nerve disorders, where DL models are currently studied for clinical applications. For further expansion of DL application in inherited optic neuropathies, we discussed the recent observational studies revealing the pathophysiological changes at the optic nerve in Leber's hereditary optic neuropathy (LHON). LHON is an inherited optic neuropathy leading to bilateral loss of vision in early age groups. Hence for early management, further footsteps in the application of DL in LHON will benefit both ophthalmologists and patients. In this review, we discuss the recent advancements of AI in the Ophthalmology and prospective of applying DL models in LHON for clinical precision and timely diagnosis.

Liver diseases are responsible for global mortality and morbidity and are a significant cause of death worldwide. Consequently, the advancement of new liver disease targets is of great interest. Non-coding RNA (ncRNA), such as microRNA (miRNA) and long ncRNA (lncRNA), has been proven to play a significant role in the pathogenesis of virtually all acute and chronic liver disorders. Recent studies demonstrated the medical applications of miRNA in various phases of hepatic pathology. PPARs play a major role in regulating many signaling pathways involved in various metabolic disorders. Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, encompassing a spectrum spanning from mild steatosis to severe non-alcoholic steatohepatitis (NASH). PPARs were found to be one of the major regulators in the progression of NAFLD. There is no recognized treatment for NAFLD, even though numerous clinical trials are now underway. NAFLD is a major risk factor for developing hepatocellular carcinoma (HCC), and its frequency increases as obesity and diabetes become more prevalent. Reprogramming anti-diabetic and anti-obesity drugs is an effective therapy option for NAFLD and NASH. Several studies have also focused on the role of ncRNAs in the pathophysiology of NAFLD. The regulatory effects of these ncRNAs make them a primary target for treatments and as early biomarkers. In this study, the main focus will be to understand the regulation of PPARs through ncRNAs and their role in NAFLD.

The human papillomavirus (HPV), commonly documented as the cause of warts, has gained much interest recently due to its possible links to several types of cancer. HPV infection is discussed in this review from multiple angles, including its virology, epidemiology, etiology, immunology, clinical symptoms, and treatment. Recent breakthroughs in molecular biology have led to the development of new methods for detecting and treating HPV in tissue. There is no cure for HPV, and although vaccines are available to prevent infection with the most common HPV viruses, their utilization is limited. Destruction and excision are the primary treatment modalities. This review sheds light on the epidemiology, molecular pathogenesis, the association of several other pathogens with HPV, the latest treatment strategies available to treat the same, and an overview of the progress made and the obstacles still to be overcome in the fight against HPV infection.

Parkinson’s disease (PD) is a complex neurodegenerative disorder, where its prevalence do vary geographically. We observed a 54-year-old male who belongs to a tribal community from Tamil Nadu, India, was diagnosed with PD. Occupationally, he was a farmer exposed to pesticides in agricultural fields. The family history revealed that the patient's parents had a consanguineous marriage and that his father showed symptoms of tremor and bradykinesia along with memory loss. We initially examined the family history and assessed Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (HY) scaling which showed low UPDRS rate and stage 3 HY scaling. Further, we conducted the dopamine transporter imaging which revealed decreased tracer binding in the left caudate with negligible uptake in the left putamen. Furthermore, we found that the patient had low levels of uric acid (2.2 mg/dL) with SNCA mutation (A53T). Environmental factors such as pesticides and smoking might have contributed SNCA mutation with low levels of uric acid. Also, the chromosomal analysis using fluorescent in situ hybridization (FISH) technique showed 22q11.2 deletion which is very uncommon in late-onset PD. In conclusion, this case study revealed that there is a humongous role of both environmental exposures and genetics in the onset of the PD.

Cancer immunotherapy moderates the immune system’s ability to fight cancer. Due to its extreme complexity, scientists are working to put together all the puzzle pieces to get a clearer picture of the immune system. Shreds of available evidence show the connection between cancer and the immune system. Immune responses to tumors and lymphoid malignancies are influenced by B cells, γδT cells, NK cells, and dendritic cells (DCs). Cancer immunotherapy, which encompasses adoptive cancer therapy, monoclonal antibodies (mAbs), immune checkpoint therapy, and CART cells, has revolutionized contemporary cancer treatment. This article reviews recent developments in immune cell regulation and cancer immunotherapy. Various options are available to treat many diseases, particularly cancer, due to the progress in various immunotherapies, such as monoclonal antibodies, recombinant proteins, vaccinations (both preventative and curative), cellular immunotherapies, and cytokines.

Oral cancer is a significant non-communicable disease affecting both emergent nations and developed countries. Squamous cell carcinoma of the head and neck represent the eight major familiar cancer types worldwide, accounting for more than 350,000 established cases every year. Oral cancer is one of the most exigent tumors to control and treat. The survival rate of oral cancer is poor due to local invasion along with recurrent lymph node metastasis. The tumor microenvironment contains a different population of cells, such as fibroblasts associated with cancer, immune-infiltrating cells, and other extracellular matrix non-components. Metastasis in a primary site is mainly due to multifaceted progression known as epithelial-to-mesenchymal transition (EMT). For the period of EMT, epithelial cells acquire mesenchymal cell functional and structural characteristics, which lead to cell migration enhancement and promotion of the dissemination of tumor cells. The present review links the tumor microenvironment and the role of EMT in inflammation, transcriptional factors, receptor involvement, microRNA, and other signaling events. It would, in turn, help to better understand the mechanism behind the tumor microenvironment and EMT during oral cancer.

Heavy metals and metalloids like cadmium, arsenic, mercury, and lead are frequently found in the soil, water, food, and atmosphere; trace amounts can cause serious health issues to the human organism. These toxic trace elements (TTE) affect almost all the organs, mainly the heart, kidney, liver, lungs, and the nervous system, through increased free radical formation, DNA damage, lipid peroxidation, and protein sulfhydryl depletion. This work aims to advance our understanding of the mechanisms behind lipid accumulation via increased free fatty acid levels in circulation due to TTEs. The increased lipid level in the myocardium worsens the heart function. This dysregulation of the lipid metabolism leads to damage in the structure of the myocardium, inclusive fibrosis in cardiac tissue, myocyte apoptosis, and decreased contractility due to mitochondrial dysfunction. Additionally, it is discussed herein how exposure to cadmium decreases the heart rate, contractile tension, the conductivity of the atrioventricular node, and coronary flow rate. Arsenic may induce atherosclerosis by increasing platelet aggregation and reducing fibrinolysis, as exposure interferes with apolipoprotein (Apo) levels, resulting in the rise of the Apo-B/Apo-A1 ratio and an elevated risk of acute cardiovascular events. Concerning mercury and lead, these toxicants can cause hypertension, myocardial infarction, and carotid atherosclerosis, in association with the generation of free radicals and oxidative stress. This review offers a complete overview of the critical factors and biomarkers of lipid and TTE-induced cardiotoxicity useful for developing future protective interventions.

Abstract Background Heat shock proteins (Hsps) are widely reported in normal cellular dynamics under stress and non-stress conditions, and parallelly, the studies regarding its role in disease condition are also progressing steadily. The function of Hsps in neurodegenerative disorders is puzzling and not fully understood. This review aims to focus on the role of Hsp27 in normal and diseased conditions and emphasize its therapeutic potential. Hsp27 Hsp27, in particular, has shown to be involved in cell viability and actin cytoskeleton remodeling and also shown to improve many disease conditions. Phosphorylated Hsp27 modulates the p53 pathway by downregulating cellular senescence and also lowers reactive oxygen species to protect TNFα-mediated apoptosis. Hsp27 is also known to interfere with mitochondria-dependent and mitochondria-independent cell apoptotic stimulation. Conclusion This article will highlight the various functions of Hsp27 especially as an anti-apoptotic factor and stress response factor and its therapeutic potential in preventing neuronal apoptosis in neurological diseases. This review also includes a comparison of the therapeutic potential of Hsp27 with regard to other small Hsps.

Abstract Background The Cochrane Collection reviews of randomized clinical trials (RCT) showed a favorable result of music therapy (MT) on individuals with autism spectrum disorder (ASD) compared with a placebo treatment. Objective This study focuses on accessing whether MT can improve the development of social skills of autistic children and to check if the effects of MT are long lasting. Materials and methods This study was designed as a pre-test/post-test and follow-up among the autistic children. Fifty-four children with mild to severe autism were selected and assigned into two groups: active and passive. The children received MT for 3 months and the groups were followed-up for 3 months. The data were analyzed with IBM-SPSS-21 software using t test and the groups were compared by analysis of covariance. Results The results of the MT intervention were mostly apparent in the following subscales—understanding/perspective-taking, initiating interactions, responding initiation, and maintaining interactions with others. The post-test covariance analysis results showed a significant increase in social skills’ scores (p

Abstract Background Radiotherapy (RT) is the chief nonsurgical method to control malignant tumors. RT has advanced in both methodological and biological aspects over the past few decades. Though RT is a momentous adjuvant non-invasive technique, it leaves behind some unsympathetic effects. Research is going on to surmount these pessimistic sides of RT. Methods We made a mini review of recent articles from the period of 2000 to 2017 regarding radiotherapy and its side effects in various types of cancers. The literature review was done by searching in PUBMED, MEDLINE, and SCOPUS. Results Here, we spotlight the physiological and genetic risks associated with the cancer patients undergoing RT. We illustrated the course of RT in most prevalent cancers tailored with dosage distribution. Radiation-induced mutation in the patients undergoing RT has been shown with evidence. Further, the major drawbacks like the development of radiation resistance in cancerous cells and secondary malignancies have been discussed. The problems associated with radiation dosage in terms of infertility and rejuvenation of reproductive cells has also been discussed. Finally, we discussed the latest treatment stratagem of RT in cancer. Conclusion Cancer treatment will not be accomplished devoid of radiotherapy. But we can brace RT using radiosensitizers and ayurvedic radioprotectors.

In recent history, immunotherapy has become a viable cancer therapeutic option. However, over many years, its tenets have changed, and it now comprises a range of cancer-focused immunotherapies. Clinical trials are currently looking into monotherapies or combinations of medicines that include immune checkpoint inhibitors (ICI), CART cells, DNA vaccines targeting viruses, and adoptive cellular therapy. According to ongoing studies, the discipline should progress by incorporating patient-tailored immunotherapy, immune checkpoint blockers, other immunotherapeutic medications, hormone therapy, radiotherapy, and chemotherapy. Despite significantly increasing morbidity, immunotherapy can intensify the therapeutic effect and enhance immune responses. The findings for the immunotherapy treatment of advanced prostate cancer (PCa) are compiled in this study, showing that is possible to investigate the current state of immunotherapy, covering new findings, PCa treatment techniques, and research perspectives in the field’s unceasing evolution.

A unique green approach has been used to limit the toxicity of AgNPs to public health and environment using Gloriosa superba (L.) methanol leaf extract which has proven against DLA tumor cells. Uncapped AgNPs are toxic, but encapsulated AgNPs with active functional groups of colchicines of methanolic extract of G. superba leaf are not cytotoxic. Capping of AgNPs by methanolic extract of G. superba leaf confirmed with phytochemical screening, UV–visible, FTIR, TEM, DLS, zeta-potential and XRD analysis. Evaluating in vitro and in vivo antitumor activity of AgNPs and methanol leaf extract was done. The leaf extract turns from yellowish brown to dark brown color by UV Visible spectroscopy, which indicates the presence of AgNPs. Stabilization and encapsulation of AgNPs by colchicines (alkaloid) was confirmed with FTIR spectra. Single crystalline nature of AgNPs was proved with XRD analysis and the zeta potential of AgNPs was found to be −27.0 mV. In vitro antitumor activity confirmed that, AgNPs were found to be the potential cytotoxic agent, with induced apoptotic activity to DLA tumor cells compared with methanol leaf extract. In vivo studies with increased average life span and normal hepatic cellular architecture by treating DLA induced Swiss albino mice with the ED50 values of 80 μg and 77 μg of G. superba leaf extract and AgNPs. In conclusion, the robustic outcome of this study would help to fabricate the herbal based nonmaterial's will reduce the toxicity of silver nanoparticles by the encapsulation of -CH2-, –CO –and –NH2– groups of G. superba leaf. Therefore, these findings will be helpful to find an optimistic new generation of silver nanoparticles based antitumor activities. Keywords: AgNP, TEM, XRD, Zeta, G.superba, DLA

Abstract Background Prader-Willi syndrome (PWS) is commonly associated with severe obesity and type 2 diabetes mellitus (T2DM) and is caused by excessive eating. Only very few studies have reported the relationship between excessive eating, weight gain, and T2DM associated with PWS. The aim of the present study was to investigate the relationship between high carbohydrate intake, body mass index (BMI), and the associated risk factor of T2DM development in people with PWS. We collected data from 23 PWS patients along with obesity control (OC) in Tamil Nadu, India. All PWS patients had T2DM whereas only 7 of 23 OC subjects had T2DM. The physical and biochemical parameters were compared in both subjects. We estimated daily intake in grams of food and calories for each item consumed by both PWS and OC subjects (with and without T2DM). Additionally, we compared BMI values and macronutrients, to investigate the occurrence of T2DM in PWS. Results All statistical analyses were done using mean ± SD. PWS subjects showed BMI values that were extremely significant in both adolescent and adult (p value 300 g by PWS patients in Tamil Nadu with BMI ≥ 30 kg/m2 as a risk factor for T2DM. We highly recommend the optimal daily intake of white rice to prevent the development of T2DM in PWS.

Parkinson's disease (PD) is a complex multi-factorial neurodegenerative disorder where various altered metabolic pathways contribute to the progression of the disease. Tryptophan (TRP) is a major precursor in kynurenine pathway (KP) and it has been discussed in various in vitro studies that the metabolites quinolinic acid (QUIN) causes neurotoxicity and kynurenic acid (KYNA) acts as neuroprotectant respectively. More studies are also focused on the effects of other KP metabolites and its enzymes as it has an association with ageing and PD pathogenesis. Until now, very few studies have targeted the role of genetic mutations in abnormal KP metabolism in adverse conditions of PD. Therefore, the present review gives an updated research studies on KP in connection with PD. Moreover, the review emphasizes on the urge for the development of biomarkers and also this would be an initiative in generating an alternative therapeutic approach for PD.

The ever-increasing rate of pollution has attracted considerable interest in research. Several anthropogenic activities have diminished soil, air, and water quality and have led to complex chemical pollutants. This review aims to provide a clear idea about the latest and most prevalent pollutants such as heavy metals, PAHs, pesticides, hydrocarbons, and pharmaceuticals—their occurrence in various complex mixtures and how several environmental factors influence their interaction. The mechanism adopted by these contaminants to form the complex mixtures leading to the rise of a new class of contaminants, and thus resulting in severe threats to human health and the environment, has also been exhibited. Additionally, this review provides an in-depth idea of various in vivo, in vitro, and trending biomarkers used for risk assessment and identifies the occurrence of mixed contaminants even at very minute concentrations. Much importance has been given to remediation technologies to understand our current position in handling these contaminants and how the technologies can be improved. This paper aims to create awareness among readers about the most ubiquitous contaminants and how simple ways can be adopted to tackle the same.

Drug studies on Rett syndrome (RTT) have drastically increased over the past few decades. This review aims to provide master data on bench-to-bedside drug studies involving RTT. A comprehensive literature review was performed by searching in PUBMED, MEDLINE and Google Scholar, international, national and regional clinical trial registries and pharmaceutical companies using the keywords "Rett syndrome treatment and/or drug or compound or molecule". Seventy drugs were investigated in non-clinical (N = 65 animal/cell line-based studies; N = 5 iPSC-based study) and clinical trials (N = 34) for ameliorating the symptoms of RTT. Though there is good progress in both clinical and non-clinical studies, none of these drugs entered phase III/IV for being launched as a therapeutic agent for RTT.