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Several chemotherapeutics against breast cancer are constrained by their adverse effects and chemoresistance. The development of novel chemotherapeutics to target metastatic breast cancer can bring effective clinical outcomes. Many breast cancer patients present with tumors that are positive for estrogen receptors (ERs), highlighting the importance of targeting the ER pathway in this particular subtype. Although selective estrogen receptor modulators (SERMs) are commonly used, their side effects and resistance issues necessitate the development of new ER-targeting agents. In this study, we report that a newly synthesized compound, TTP-5, a hybrid of pyrimidine, triazole, and tert-butyl-piperazine-carboxylate, effectively binds to estrogen receptor alpha (ERα) and suppresses breast cancer cell growth. We assessed the impact of TTP-5 on cell proliferation using MTT and colony formation assays and evaluated its effect on cell motility through wound healing and invasion assays. We further explored the mechanism of action of this novel compound by detecting protein expression changes using Western blotting. Molecular docking was used to confirm the interaction of TTP-5 with ERα. The results indicated that TTP-5 significantly reduced the proliferation of MCF-7 cells by blocking the ERα signaling pathway. Conversely, although it did not influence the growth of MDA-MB-231 cells, TTP-5 hindered their motility by modulating the expression of proteins associated with epithelial-mesenchymal transition (EMT), possibly via the Wnt/ß-catenin pathway.

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Background: Tracheal, Bronchus, and Lung (TBL) cancer continues to represent the majority of cancer-related incidence and mortality in United States (U.S.). While air pollutants are considered essential risk factors, both global and national average concentrations of major harmful air pollutants have significantly decreased over the decades. Green space may have a beneficial effect on human health. Methods: We obtained data on national and state-level burden of TBL cancer, the annual average concentration of main air pollutants, and levels of green spaces in 2007, 2013, and 2019. According to generalized estimating equation (GEE), we examine the associations among incidence and mortality of TBL cancer, air pollutants, and greenspaces, represented by the Normalized Difference Vegetation Index (NDVI) in different age groups with models adjusted with meteorological, and socio-demographic. We observed additional effects of the interaction between the NDVI, Ozone, PM2.5, and other factors, which helped us to interpret and understand our results. Also, we collated states that witnessed net increments in forest coverage and conducted the same analysis separately. Results: In our analysis, the majority of associations between NDVI and air pollutants with TBL cancer remained significantly positive, particularly noticeable among individuals aged 20 to 54. However, our findings did not explore air pollution as a potential mediator between greenspace exposure and TBL cancer. While the associations of PM2.5 with TBL cancer remained positive, the other four pollutants showed positive but statistically insignificant associations. Our interaction analysis yielded that there were positive associations between NDVI and ozone, PM2.5, and tobacco use. Max NDVI acts as a protective factor along with high HDI. Additionally, PM2.5 and HDI also showed a negative association. In 18 states with more forest, NDVI acts as a protective factor along with higher health care coverage, better health status, and participation in physical activities. Conclusion: In the state-level of U.S., the effects of total greenspace with TBL cancer are mixed and could be modified by various socio-economic factors. PM2.5 has a direct correlation with TBL cancer and the effects can be influenced by underlying socioeconomic conditions.

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Background: The incidence and mortality of gynaecological cancers can significantly impact women's quality of life and increase the health care burden for organisations globally. The objective of this study was to evaluate global inequalities in the incidence and mortality of gynaecological cancers in 2022, based on The Global Cancer Observatory (GLOBOCAN) 2022 estimates. The future burden of gynaecological cancers (GCs) in 2050 was also projected. Methods: Data regarding to the total cases and deaths related to gynaecological cancer, as well as cases and deaths pertaining to different subtypes of GCs, gathered from the GLOBOCAN database for the year 2022. Predictions for the number of cases and deaths in the year 2050 were derived from global demographic projections, categorised by world region and Human Development Index (HDI). Results: In 2022, there were 1 473 427 new cases of GCs and 680 372 deaths. The incidence of gynecological cancer reached 30.3 per 100 000, and the mortality rate hit 13.2 per 100 000. The age-standardised incidence of GCs in Eastern Africa is higher than 50 per 100 000, whereas the age-standardised incidence in Northern Africa is 17.1 per 100 000. The highest mortality rates were found in East Africa (ASMR (age-standardised mortality rates) of 35.3 per 100 000) and the lowest in Australia and New Zealand (ASMR of 8.1 per 100 000). These are related to the endemic areas of HIV and HPV. Very High HDI countries had the highest incidence of GCs, with ASIR (age-standardised incidence rates) of 34.8 per 100 000, and low HDI countries had the second highest incidence rate, with an ASIR of 33.0 per 100 000. Eswatini had the highest incidence and mortality (105.4 per 100 000; 71.1 per 100 000) and Yemen the lowest (5.8 per 100 000; 4.4 per 100 000). If the current trends in morbidity and mortality are maintained, number of new cases and deaths from female reproductive tract tumours is projected to increase over the next two decades. Conclusions: In 2022, gynaecological cancers accounted for 1 473 427 new cases and 680 372 deaths globally, with significant regional disparities in incidence and mortality rates. The highest rates were observed in Eastern Africa and countries with very high and low HDI, with Eswatini recording the most severe statistics. If current trends continue, the number of new cases and deaths from gynaecological cancers is expected to rise over the next two decades, highlighting the urgent need for effective interventions.

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Haematopoiesis within the bone marrow (BM) represents a complex and dynamic process intricately regulated by neural signaling pathways. This delicate orchestration is susceptible to disruption by factors such as aging, diabetes, and obesity, which can impair the BM niche and consequently affect haematopoiesis. Genetic mutations in Tet2, Dnmt3a, Asxl1, and Jak2 are known to give rise to clonal haematopoiesis of intermediate potential (CHIP), a condition linked to age-related haematological malignancies. Despite these insights, the exact roles of circadian rhythms, sphingosine-1-phosphate (S1P), stromal cell-derived factor-1 (SDF-1), sterile inflammation, and the complement cascade on various BM niche cells remain inadequately understood. Further research is needed to elucidate how BM niche cells contribute to these malignancies through neural regulation and their potential in the development of gene-corrected stem cells. This literature review describes the updated functional aspects of BM niche cells in haematopoiesis within the context of haematological malignancies, with a particular focus on neural signaling and the potential of radiomitigators in acute radiation syndrome. Additionally, it underscores the pressing need for technological advancements in stem cell-based therapies to alleviate the impacts of immunological stressors. Recent studies have illuminated the microheterogeneity and temporal stochasticity of niche cells within the BM during haematopoiesis, emphasizing the updated roles of neural signaling and immunosurveillance. The development of gene-corrected stem cells capable of producing blood, immune cells, and tissue-resident progeny is essential for combating age-related haematological malignancies and overcoming immunological challenges. This review aims to provide a comprehensive overview of these evolving insights and their implications for future therapeutic strategies.

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Background: Impact of radiotherapy (RT) for esophageal cancer (EC) patients on the development of secondary head and neck cancer (SHNC) remains equivocal. The objective of this study was to investigate the link between definitive RT used for EC treatment and subsequent SHNC. Methods: This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of primary EC patients. Fine-Gray competing risk regression and standardized incidence ratio (SIR) and propensity score matching (PSM) method were used to match SHNC patients with only primary head and neck cancer (HNC) patients. Overall survival (OS) rates were applied by Kaplan-Meier analysis. Results: In total, 14,158 EC patients from the SEER database were included, of which 9,239 patients (65.3%) received RT and 4,919 patients (34.7%) received no radiation therapy (NRT). After a 12-month latency period, 110 patients (1.2%) in the RT group and 36 patients (0.7%) in the NRT group experienced the development of SHNC. In individuals with primary EC, there was an increased incidence of SHNC compared to the general US population (SIR = 5.95, 95% confidence interval (CI): 5.15 - 6.84). Specifically, the SIR for SHNC was 8.04 (95% CI: 6.78 - 9.47) in the RT group and 3.51 (95% CI: 2.64 - 4.58) in the NRT group. Patients who developed SHNC after RT exhibited significantly lower OS compared to those after NRT. Following PSM, the OS of patients who developed SHNC after RT remained significantly lower than that of matched patients with only primary HNC. Conclusion: An association was discovered between RT for EC and increased long-term risk of SHNC. This work enables radiation oncologists to implement mitigation strategies to reduce the long-term risk of SHNC in patients who have received RT following primary EC.

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BACKGROUND: Neurosurgical interventions and trauma are common causes of damage to the optic nerve. This determines the relevance of research for solutions aimed at restoration of the nerve's anatomical integrity, electrical conductivity, and subsequently - restoration of its function. Restore a damaged (cut) optic nerve using n. suralis autograft in vivo. METHODS: The experiment involved reconstruction of the optic nerve through injury modulation, graft placement and restored nerve harvest and evaluation. Injury modulation included removal of a fragment of the optic nerve. Autograft harvesting and placement involved resection of a fragment of the sural (sensory) nerve and its subsequent anastomosis in place of the removed fragment of the optic nerve. As an experimental model, a rabbit of the "Burgundy" breed was used. The animal was previously examined for the presence of infectious and other diseases to confirm its health. RESULTS: Four months post operatively when stimulating the operated right eye, low-amplitude components altered in shape are registered. Thus, signs of mild restoration of electrical conductivity on the treated optic nerve were seen. CONCLUSIONS: Our initial experience shows the technical feasibility of reconstructing the optic nerve using an autograft, the possibility of axonal growth through the graft and, in the future, using this method for direct optic nerve reconstruction, as well as a bypass method for damage to the optic nerve with various tumor diseases of the optic nerve, tumors of the chiasmatic-sellar localization, orbital injuries.

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Autophagy is a cellular catabolic process characterized by the formation of double-membrane autophagosomes. Transmission electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation. A large number of studies have shown that autophagy is closely related to the digestion, secretion, and regeneration of gastrointestinal (GI) cells. However, the role of autophagy in GI diseases remains controversial. This article focuses on the morphological and biochemical characteristics of autophagy in GI diseases, in order to provide new ideas for their diagnosis and treatment.

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INTRODUCTION: Metformin, a biguanide on the WHO's list of essential medicines has a long history of 50 years or more in treating hyperglycemia, and its therapeutic saga continues beyond diabetes treatment. Glucoregulatory actions are central to the physiological effects of metformin; surprisingly, the precise mechanism with which metformin regulates glucose metabolism is not thoroughly understood yet. METHOD: The main aim of this review is to explore the recent implications of metformin in hepatic gluconeogenesis, AMPKs, and SHIP2 and subsequently to elucidate the metformin action across intestine and gut microbiota. We have searched PubMed, google scholar, Medline, eMedicine, National Library of Medicine (NLM), clinicaltrials.gov (registry), and ReleMed for the implications of metformin with its updated role in AMPKs, SHIP2, and hepatic gluoconeogenesis, and gut microbiota. In this review, we have described the efficacy of metformin as a drug repurposing strategy in modulating the role of AMPKs and lysosomal-AMPKs, and controversies associated with metformin. RESULT: Research suggests that biguanide exhibits hormetic effects depending on the concentrations used (micromolar to millimolar). The primary mechanism attributed to metformin action is the inhibition of mitochondrial complex I, and subsequent reduction of cellular energy state, as observed with increased AMP or ADP ratio, thereby metformin can also activate the cellular energy sensor AMPK to inhibit hepatic gluconeogenesis. However, new mechanistic models have been proposed lately to explain the pleiotropic actions of metformin; at low doses, metformin can activate lysosomal-AMPK via the AXIN-LKB1 pathway. Conversely, in an AMPK-independent mechanism, metformin-induced elevation of AMP suppresses adenylate cyclase and glucagon-activated cAMP production to inhibit hepatic glucose output by glucagon. Metformin inhibits mitochondrial glycerophosphate dehydrogenase; mGPDH, and increases the cytosolic NADH/NAD+, affecting the availability of lactate and glycerol for gluconeogenesis. Metformin can inhibit Src homology 2 domain-containing inositol 5-phosphatase 2; SHIP2 to increase the insulin sensitivity and glucose uptake by peripheral tissues. CONCLUSION: In addition, new exciting mechanisms suggest the role of metformin in promoting beneficial gut microbiome and gut health; metformin regulates duodenal AMPK activation, incretin hormone secretion, and bile acid homeostasis to improve intestinal glucose absorption and utilization.

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Previous studies described that asthma patients who received corticosteroid therapy have been constrained by the corticosteroid resistance subsequently fostered to severe refractory asthma. In this review, we discussed the implications of TSLP, RXR, the role of STAT5-activating cytokines, and IL-33/NH-cell signaling pathways, and recent clinical evidence on TSLP blockers in steroid-resistant asthma. We have searched several public databases such as Pubmed, Scopus, and Relemed and obtained information pertinent to the TSLP, RXR, TSLP blockers, the STAT5-activating cytokines, and IL-33. We discussed the multiple cell signaling mechanisms underlying steroid resistance. Blocking the TSLP and other key signaling molecules like STAT5 can retrieve the sensitivity of natural helper-cells to corticosteroids. RXR derivatives treatment can modulate the activity of TSLP, which further modulates steroid resistance in severe asthmatic patients and in patients with refractory asthma. We discussed the steroid-resistance mediated by the Th2 cells and Th2-driven eosinophilia upon corticosteroid intake. Thus, this review will be beneficial for clinicians and molecular biologists to explore the inflammatory pathways associated with refractory asthma conditions and develop novel therapies against corticosteroid-resistant asthma.

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Background: The rapid spread of SARS-COV-2, characterized by its severe course in the absence of effective specific treatment for this infection, may become a significant risk factor for psycho-emotional disorders' emergence during this pandemic. One of the vulnerable groups in the current situation are first-year medical students, whose problems associated with an unfavorable sanitary-epidemiological situation and an increased infection risk are compounded by the difficulties of adapting to specific professional environments. In this situation, along with strict adherence to nonspecific prevention methods, the mass student SARS-COV-2 vaccination acquires particular importance. Objective: To compare the attitudes of first-year medical students in Russia and Azerbaijan toward SARS-COV-2 immunization and to assess the vaccination impact on the student's psycho-emotional state during the SARS-COV-2 pandemic. Materials and Methods: The study involved 594 first-year students at the Moscow and Baku branches of Sechenov University. The Google Forms platform was used to conduct an anonymous sociological survey. To compare the psychoemotional state of vaccinated freshmen and non-vaccinated students, we used the State-Trait Anxiety Inventory, STAI, to assess reactive anxiety and the Beck Depression Inventory test - to diagnose depressive symptoms. The online survey was conducted during the fourth wave of coronavirus infection. WHO official sources were used to analyze the current epidemiological SARS-COV-2 situation during the study data provided by the Russian Federal Service on Customers' Rights Protection and Human Well-Being Surveillance and JHU CSSE. Statistical analysis was carried out using RStudio. Results: The study results showed that vaccination coverage of first-year students at the Moscow branch of Sechenov University during the fourth wave of the SARS-COV-2 pandemic was 42,9±5,13%, at the Baku branch - 69,6±5,86%. The lack of reliable information about anticovid vaccines, indicated by a third of all respondents, may largely determine the motivated participation in the vaccination SARS-COV-2 campaign. The role of medical school in imparting knowledge about active SARS-COV-2 immunization to medical students was found to be insignificant. It was shown that the percentage of students willing to recommend SARS-COV-2 vaccination to the people around them and thereby contribute to increasing collective immunity level significantly depends on the percentage of students vaccinated. It was proved that vaccinated students were characterized by significantly greater psychological stability regardless of their study place. Conclusion: Vaccination is not only a good preventive measure against the infection spread but also a significant factor in stabilizing the psycho-emotional state of first-year students, which significantly affects the quality of their educational process and its effectiveness.

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Objective: To evaluate the current status of trial registration on the Chinese Clinical Trial Registry (ChiCTR). Design: In this descriptive study, a multi-dimensional grouping analysis was conducted to estimate trends in the annual trial registration, geographical distribution, sources of funding, targeted diseases, and trial subtypes. Setting: We have analyzed all clinical trial records (over 30,000) registered on the Chinese Clinical Trial Registry (ChiCTR) from 2007 to 2020 executed in China. Main outcomes and measures: The main outcome was the baseline characteristics of registered trials. These trials were categorized and analyzed based on geographical distribution, year of implementation, disease type, resource and funding type, trial duration, trial phase, and the type of experimental approach. Results: From 2008 to 2017, a consistent upward trend in clinical trial registrations was observed, showing an average annual growth rate of 29.2%. The most significant year-on-year (yoy%) growth in registrations occurred in 2014 (62%) and 2018 (68.5%). Public funding represented the predominant source of funding in the Chinese healthcare system. The top five ChiCTR registration sites for all disease types were highly populated urban regions of China, including Shanghai (5,658 trials, 18%), Beijing (5,127 trials, 16%), Guangdong (3,612 trials, 11%), Sichuan (2,448 trials, 8%), and Jiangsu (2,196 trials, 7%). Trials targeting neoplastic diseases accounted for the largest portion of registrations, followed by cardio/cerebrovascular disease (CCVD) and orthopedic diseases-related trials. The largest proportions of registration trial duration were 1-2 years, less than 1 year, and 2-3 years (at 27.36, 26.71, and 22.46%). In the case of the research phase, the top three types of all the registered trials are exploratory research, post-marketing drugs, and clinical trials of new therapeutic technology. Conclusion and relevance: Oncological and cardiovascular diseases receive the highest share of national public funding for medical clinical trial-based research in China. Publicly funded trials represent a major segment of the ChiCTR registry, indicating the dominating role of public governance in this health research sector. Furthermore, the growing number of analyzed records reflect the escalation of clinical research activities in China. The tendency to distribute funding resources toward exceedingly populated areas with the highest incidence of oncological and cardiovascular diseases reveals an aim to reduce the dominating disease burden in the urban conglomerates in China.

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Lactoferrin (LF) is a protein molecule with a wide variety of physiological properties. LF has broadspectrum antibacterial, antiviral, antioxidant, and antitumor, and possesses immunomodulatory properties to regulate immunity and gastrointestinal function. The main aim of this review is to explore the recent investigations on the functional role of LF against several human disorders and diseases through monotherapy or combinatorial regimens with other biological/chemotherapeutic agents through novel nanoformulations. We significantly searched public databases such as Pubmed, National Library of Medicine, relemed, Scopus and collected published reports pertaining to these recent reports on lactoferrin as a monotherapy or combination therapy, and its nanoformulations. We have discussed vividly the role of LF as a growth factor with substantial potential that can promote cell growth and regeneration potential for repairing tissues such as bone, skin, mucosa, and tendons. In addition, we have discussed novel perspectives on the role of LF as an inductive factor for the proliferation of stem cells in tissue recovery and discussed its novel modulating effects in ameliorating cancer and microbial growth through several signaling cascades via monotherapy or combinatorial regimens. Furthermore, the regeneration potential of this protein is reviewed to explore the efficacy and prospects of new treatment methods. This review benefits various microbiologists, stem cell therapists, and oncologists to explore the efficacy of LF in several segments of medicine by examining its ability as a stem cell differentiation factor, and anticancer agent or antimicrobial agent through novel formulations in preclinical or clinical study.

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BACKGROUND: Optimal physical activity is known to reduce cardiovascular, respiratory and endocrine system diseases and, as a consequence, improve quality of life. An important risk factor for reinjuries during normal exercise is the initial connective tissue pathology. The variety of clinical dysplastic manifestations significantly complicate the timely diagnosis of this comorbidity. AIM: To establish pathognomonic sex-specific dysplasia phenotypes that indicate a particular sensitivity to physical exertion. METHODS: The study involved 117 participants with recurrent musculoskeletal injuries that occurred during normal exercise. There were 67 women (57.26%) and 50 men (42.74%), which made it possible to compare the presence of the identified signs between sexes. A validated questionnaire was used to screen their connective tissue status. RESULTS: Ranking the most commonly revealed dysplasia signs depending on their clinical significance made it possible to establish pathognomonic sex-specific phenotypes that indicated a particular susceptibility to injuries. Individualized programs of optimal physical activity are necessary for men with chest deformities, flat-valgus feet, dolichostenomelia, arachnodactylia, hemorrhoids, abdominal muscle diastasis and recurrent hernias. In women, special sensitivity to physical exertion was associated with a combination of signs such as asthenic body, joint hypermobility, overly soft auricles, thin hyperelastic skin, atrophic striae, telangiectasias and varicose veins. Of particular importance were universal signs such as gothic palate, scoliosis, kyphosis, leg deformities, temporomandibular joint crunching, and moderate to high myopia. CONCLUSION: Participants' connective tissue condition should be considered when designing optimal physical activity programs. Identifying the established sex-specific dysplasia phenotypes will allow timely optimization of training loads, thus reducing the risk of injury.

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Sera obtained from convalescent individuals, and vaccinated individuals can induce low neutralizing efficacy against variants of concerns (VOCs) of SARS-CoV-2. In addition, the majority of COVID-19 vaccines are less efficacious against VOCs when compared to their efficacy against the original virus. Immune escape is one of the significant mechanisms observed during SARS-CoV-2 infection due to the substantial mutational capacity of VOCs such as B.1.1.7, P.1, B.1.351, B.1.617.2, C.37, and B.1.621. Omicron, a novel strain of SARS-CoV-2, also referred to as B.1.1.529, was identified in South Africa. This variant is a potential new VOC by the World Health Organization (WHO), and confirmed cases have been arising across several nations due to its rapid spreading ability. Omicron variant can acquire substantial immune escape following Delta, Beta/Gamma D614G VOCs and subsequently facilitating potential infectivity due to its enhanced ACE2 binding ability. The Omicron variant is a highly mutated variant accompanied by higher transmissibility and immune evasion. This mini review describes the ability of VOCs to acquire immune escape and also describes the comparative neutralization efficacy of several vaccines, including Booster doses against SARS-CoV-2.

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Several research reports delineated the significant role of miRNAs in cancer proliferation, and their modulatory role in cancer mitigation, and drug resistance. Melanoma cells have been acquiring stemness to several chemotherapeutic agents through drug efflux proteins, epigenetic modulation, and DNA repair. miRNAs could be applied as novel therapeutic modalities for treating several kinds of cancers to modulate these mechanisms involved in stemness. Nanocarriers to carry these tumor-targeting miRNAs to modulate stemness are a prominent strategy to overcome their low penetrability, minimal stability, and nonspecificity. We have searched several public databases such as PubMed, Medline, Google scholar, and NLM and obtained the information pertinent to the miRNA-based nanocarrier systems to target stemness through epigenetic modulation in melanomas. This review delineates that various miRNAs can modulate the stemness in melanomas by specific intricate epigenetic signaling, and other cell-based signaling mechanisms. Specific nanocarrier formulations with specific miRNAs are optimal methods to deliver these miRNAs in order to achieve significant entrapment efficiency, loading efficiency, and stability. Furthermore, the combinatorial regimen of FDA-approved chemotherapeutic molecules with tumor-targeting miRNAs and chemotherapy combined with nanocarriers can efficiently deliver the utmost therapeutic window by targeting tumor matrix, invasion, metastasis, and angiogenesis in melanomas. Substantial research should focus on the clinical application of this gene therapy in melanomas using these low immunogenic, highly degradable, and biocompatible combinatorial nanotherapeutic regimens.

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BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is causing a high mortality rate due to the lack of efficient early prognosis markers and suitable therapeutic regimens. The prognostic role of genes responsible for the acquisition of radioresistance in ESCC has not been fully elucidated. AIM: To establish a prognostic model by studying gene expression patterns pertinent to radioresistance in ESCC patients. METHODS: Datasets were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The edgeR, a Bioconductor package, was used to analyze mRNA expression between different groups. We screened genes specifically responsible for radioresistance to estimate overall survival. Pearson correlation analysis was performed to confirm whether the expression of those genes correlated with each other. Genes contributing to radioresistance and overall survival were assessed by the multivariate Cox regression model through the calculation of ßi and risk score using the following formula: . RESULTS: We identified three prognostic mRNAs (cathepsin S [CTSS], cluster of differentiation 180 [CD180], and SLP adapter and CSK-interacting membrane protein [SCIMP]) indicative of radioresistance. The expression of the three identified mRNAs was related to each other (r > 0.70 and P < 0.05). As to 1-year and 3-year overall survival prediction, the area under the time-dependent receiver operating characteristic curve of the signature consisting of the three mRNAs was 0.716 and 0.841, respectively. When stratifying patients based on the risk score derived from the signature, the high-risk group exhibited a higher death risk and shorter survival time than the low-risk group (P < 0.0001). Overall survival of the low-risk patients was significantly better than that of the high-risk patients (P = 0.018). CONCLUSION: We have developed a novel three-gene prognostic signature consisting of CTSS, CD180, and SCIMO for ESCC, which may facilitate the prediction of early prognosis of this malignancy.

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Polycystic ovarian syndrome (PCOS) can cause infertility in females due to hyperandrogenism and neuroendocrine abnormalities. The aim of this study is to decipher the impact of endocrine variables, hyperandogenism, insulin resistance, oxidative stress, and dietary conditions in PCOS conditions, subsequently to depict the role of epigenetic factors relative to phenotypic manifestations in PCOS conditions. We have reviewed several metabolic milieus pertinent to PCOS conditions. Comparative efficacies of various PCOS therapies, and recent clinical recommendations for the effective management of PCOS and role of metabolic/endocrine variables in PCOS conditions were described. Comparative therapeutic effects were vividly delineated according to the variable pathophysiology and internal variables during PCOS syndrome on the female body through the formation of cascade of endocrine pathology, which affects working capacity and fosters redox stress-induced cardiovascular, neural, and liver abnormalities. GLP-1 agonists, insulin sensitizers (metformin), and diet and exercise regimens efficacy were explained in enhancing the fertility outcomes among the overweight or obese females with PCOS. Comprehensive appraisal of DNA methylation as epigenetic changes and the manifestations of methylated genes in PCOS conditions were discussed particularly to screen novel molecular targets for developing efficient diagnostic indicators for predicting PCOS risk or its progression. Due to the reversible nature of epigenetic modifications, it is possible to screen the "druggable" regions to target or to correct abnormalities in the gene expression subsequently to develop chromatin-modifying therapies against PCOS.

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BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19) triggers the development of numerous pathologies and infection-linked complications and exacerbates existing pathologies in nearly all body systems. Aside from the primarily targeted respiratory organs, adverse SARS-CoV-2 effects were observed in nervous, cardiovascular, gastrointestinal/metabolic, immune, and other systems in COVID-19 survivors. Long-term effects of this viral infection have been recently observed and represent distressing sequelae recognised by the World Health Organisation (WHO) as a distinct clinical entity defined as post-COVID-19 condition. Considering the pandemic is still ongoing, more time is required to confirm post COVID-19 condition diagnosis in the COVID-19 infected cohorts, although many reported post COVID-19 symptoms overlap with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). AIMS OF REVIEW: In this study, COVID-19 clinical presentation and associated post-infection sequelae (post-COVID-19 condition) were reviewed and compared with ME/CFS symptomatology. KEY SCIENTIFIC CONCEPTS OF REVIEW: The onset, progression, and symptom profile of post COVID-19 condition patients have considerable overlap with ME/CFS. Considering the large scope and range of pro-inflammatory effects of this virus, it is reasonable to expect development of post COVID-19 clinical complications in a proportion of the affected population. There are reports of a later debilitating syndrome onset three months post COVID-19 infection (often described as long-COVID-19), marked by the presence of fatigue, headache, cognitive dysfunction, post-exertional malaise, orthostatic intolerance, and dyspnoea. Acute inflammation, oxidative stress, and increased levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNFα), have been reported in SARS-CoV-2 infected patients. Longitudinal monitoring of post COVID-19 patients is warranted to understand the long-term effects of SARS-CoV-2 infection and the pathomechanism of post COVID-19 condition.

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