Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases.

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.

Metformin Effects on SHIP2, AMPKs and Gut Microbiota: Recent Updates on Pharmacology.

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.

Novel Perspectives of TSLP and RXR Signaling in Corticosteroid-Resistant Asthma: Updates on TSLP Blockers.

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.

Vaccination as a Significant Factor Influencing the Psychoemotional State of Medical Students During the Sars-Cov-2 Pandemic: An International Aspect.

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.

Chinese Clinical Trial Registry 13-year data collection and analysis: geographic distribution, financial support, research phase, duration, and disease categories.

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.

Novel Perspectives on Nanotechnological and Biomedical Implications of Monotherapy or Combination Regimen of Lactoferrin.

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.

Identifying sex-specific injury predictors as a key factor in maintaining optimal physical activity levels.

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.

Comparative Pharmacological Efficacy of COVID-19 Vaccines against the Variants of Concerns (VOCs) of SARS-CoV-2: Recent Clinical Studies on Booster Dose.

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.

Perspectives on the nanocarriers with miRNAs for targeting melanoma stemness through epigenetic regulation.

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.

Identification of a three-gene prognostic signature for radioresistant esophageal squamous cell carcinoma.

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.

Updates on Molecular Targets and Epigenetic-Based Therapies for PCOS.

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.

Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome.

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.

Comparative clinical studies of primary chemoradiotherapy versus S-1 and nedaplatin chemotherapy against stage IVb oesophageal squamous cell carcinoma: a multicentre open-label randomised controlled trial.

INTRODUCTION: Oesophageal squamous cell carcinoma (OSCC) is one of the most commonly occurring devastating tumours worldwide, including in China. To date, the standard care of patients with stage IV OSCC is systemic chemotherapy and palliative care, which results in poor prognosis. However, no consensus has been established regarding the role of radiotherapy in targeting the primary tumour in patients with stage IVa OSCC. Thus, the aim of this study is to assess the effectiveness of primary radiotherapy combined with S-1 and nedaplatin (NPD) chemotherapy in the patients with stage IV OSCC. METHODS AND ANALYSIS: The study is a multicentre, open-label, randomised controlled trial. A total of 180 eligible patients with stage IV OSCC will be randomised into a study group (90 patients) and a control group (90 patients). Patients in the study group will receive radiotherapy to the primary tumour at a dose of 50.4 Gy combined with 4-6 cycles of S-1 and NPD chemotherapy. In the control group, patients will only receive 4-6 cycles of S-1 and NPD chemotherapy. The primary and secondary outcomes will be measured. The differences between the two groups will be statistically analysed with regard to overall survival, the progression-free survival and safety. All outcomes will be ascertained before treatment, after treatment and after the follow-up period.The results of this study will provide evidence on the role of radiotherapy in patients with stage IV OSCC in China, which will show new options for patients with advanced oesophageal cancer. ETHICS AND DISSEMINATION: This study was approved by the Institutional Ethics Committee of The First Hospital Affiliated of Zhengzhou University (approval number: SS-2018-04). TRIAL REGISTRATION: The trial has been registered at the Chinese Clinical Trial Registry (ChiCTR1800015765) on 1 November 2018; retrospectively registered, http://www.chictr.org.cn/index.aspx.

Nociceptors: Their Role in Body's Defenses, Tissue Specific Variations and Anatomical Update.

The human body is constantly under the influence of numerous pathological factors: both external and internal. These factors can be potentially harmful and are perceived as such with a specialized nervous system subunit: the nociceptive system. The functional unit of the nociceptive system is the nociceptor. Recent studies have shown that nociceptors play a crucial role in maintaining of defensive homeostasis (responsive, immune, behavioral). Nociceptors respond to potentially harmful stimuli within viscera, bones, muscles, skin and specialized sensory organs. They function as complex predictors of harm through formation of pain stimulus. Their function and structures vary within different tissues. This variability reflects the anatomical and pathological peculiarities of varying tissues. Nociceptors play a significant role in adaptive, protective and behavioral reactions. Their functional capabilities and vast spread throughout the body make them the main units of the body's defense system, allowing us to interact with the inner and outer environments.

Current Drug Targets for Gut Microbiota Biocorrection during the SARS-CoV-2 Pandemic: A Systematic Review.

The gut microbiota are known to play an important role in maintaining the body's homeostasis and increasing its immunoresistance. Their role has not been well defined in the course of SARS-CoV-2 infection. AIM: The aim of this study was to evaluate the pathogenetic relationship between gut microbiota, immunological reactivity disruption and microbiota pathologies with the new coronavirus infection's course in order to substantiate the use of current drugs correcting gut microbiota during the SARS-CoV-2 pandemic. MATERIALS AND METHODS: Electronic databases of WHO Infection Control, Global Health, ScienceDirect, Elsevier, CDC infection diseases database, Google Academy, "Scientific electronic library eLIBRARY.RU", MEDLINE, CyberLeninka, Embase, PubMed-NCBI, RSCI, Scopus, and Cochrane Library were used for this analytical research. RESULTS: The research results showed normal gut microbiota as one of the important components of a multilevel immune defense system. The intestinal microbiota support the notion of initial activation and readiness in order to induce a quick response to the invasion of pathogens, including RNA viruses, such as SARS-CoV-2. Current research suggests that the intestinal microbiota play an important role in the pathogenesis and predetermination of disease severity in COVID-19. By producing essential metabolites and neutralizing toxic substrates, symbionts regulate the functioning of all organs and systems, maintaining the body's homeostasis and immunological responses. Intestinal microbiota disorders determine the postvaccination anti-COVID immunity's efficacy, specifically the susceptibility to SARS-CoV-2 and the severity of this infection. This is done by stimulating a local intestinal immune response via secretory immunoglobulins and the acquired immunity of the microbiome. The high prevalence of dysbiosis within the populous indicates the necessity of regular gut microbiota biocorrection during the SARS-CoV-2 pandemic. Our systematic review of current biopreparations correcting gut microbiota provides a valuable reference to the practicing clinicians to quickly specify and develop a wide variety of medicines, assess their capabilities, and choose the optimal treatment for patients at risk of SARS-CoV-2 infection. CONCLUSION: Current data support the notion that gut microflora biocorrection may help increase population immunity and preserve public health during the SARS-CoV-2 pandemic.

Recent Investigations on the Functional Role of Cerebellar Neural Networks in Motor Functions & Nonmotor Functions -Neurodegeneration.

The cerebellum is a well-established primary brain center in charge of controlling sensorimotor functions and non-motor functions. Recent reports depicted the significance of cerebellum in higher-order cognitive functions, including emotion-processing, language, reward-related behavior, working memory, and social behavior. As it can influence diverse behavioral patterns, any defects in cerebellar functions could invoke neuropsychiatric diseases as indicated by the incidence of alexithymia and induce alterations in emotional and behavioral patterns. Furthermore, its defects can trigger motor diseases, such as ataxia and Parkinson's disease (PD). In this review, we have extensively discussed the role of cerebellum in motor and non-motor functions and how the cerebellum malfunctions in relation to the neural circuit wiring as it could impact brain function and behavioral outcomes in patients with neuropsychiatric diseases. Relevant data regarding cerebellar non-motor functions have been vividly described, along with anatomy and physiology of these functions. In addition to the defects in basal ganglia, the lack of activity in motor related regions of the cerebellum could be associated with the severity of motor symptoms. All together, this review delineates the importance of cerebellar involvement in patients with PD and unravels a crucial link for various clinical aspects of PD with specific cerebellar sub-regions.

Iatrogenic Glossopharyngeal Neuropathy in Aesthetic Practice: A Case Report.

Iatrogenic glossopharyngeal nerve injuries are commonly associated with procedures such as a tonsillectomy, carotid endarterectomy, and endotracheal intubation. We present a previously unreported complication of a thread lift procedure in the jowl region, causing damage to the glossopharyngeal nerve through compression. The glossopharyngeal nerve belongs to the bulbar group of the cranial nerves. It is connected with the vagus and, therefore, is closely associated with the latter functionally and anatomically. Damage to the former may present with cardiovascular complications associated with the vagus nerve. The presented case demonstrates the diagnostic and treatment aspects of iatrogenic injury to the glossopharyngeal nerve.

Testing lncRNAs signature as clinical stage-related prognostic markers in gastric cancer progression using TCGA database.

LncRNA expression can be conducive to gastric cancer (GC) prognosis. The objective of this study is to ascertain five specific lncRNAs involved in tumor progression of GC and their role as prognostic markers to diagnose clinical stage-wise GC. High-throughput RNA sequencing data were obtained from The Cancer Genome Atlas (TCGA) database and performed genome-wide lncRNA expression analysis using edgeR package, Bioconductor.org, and R-statistical computing to analyze differentially expressed lncRNA analysis. Cutoff parameters were FDR < 0.05 and |Log2FC| > 2. Total 351 tumor samples with differentially expressed lncRNAs were divided into group-1 lncRNAs such as AC019117.2 and LINC00941, and group-2 lncRNAs such as LINC02410, AC012317.2, and AC141273.1 by 2:1. The Spearman correlation coefficients (p < 0.05) and correlation test function (cor.test ()) were performed for lncRNAs as per clinical stage. Cytoscape software was used to construct lncRNA-mRNA interaction networks. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway (p < 0.05) analysis were conducted using the clusterProfiler package. Kaplan-Meier survival analysis was performed to determine the overall survival of patients based on the expression of five lncRNAs in different clinical stages of GC. AC019117.2 and LINC00941 of group 1 inferred a positive correlation with clinical stages of stage I to stage IV, and their expressions were higher in tumor tissues than normal tissues. On the contrary, LINC02410, AC012317.2, and AC141273.1 of group 2 exhibited a negative correlation with clinical stage, and they exhibited more expression in normal tissues compared to tumor tissues. GO and KEGG pathway analysis reported that AC019117.2 may interact with LINC00941 via ITGA3 and trophoblast glycoprotein (TPBG) to foster tumor progression. Tumor-specific group-1 lncRNAs were conducive to the poor overall survival and exhibited a positive correlation with the clinical stages of stage I to stage IV in GC as per the lncRNA-mRNA networking analysis. These five lncRNAs could be considered as clinically useful lncRNA-based prognostic markers to predict clinical stage-wise GC progression.