Search

Dietary nutrients are associated with the development of cardiovascular disease (CVD) both through traditional pathways (inducing hyperlipidemia and chronic inflammation) and through the emergence of a metaorganism-pathogenesis pathway (through the gut microbiota, its metabolites, and host). Several molecules from food play an important role as CVD risk-factor precursors either themselves or through the metabolism of the gut microbiome. Animal-based dietary proteins are the primary source of CVD risk-factor precursors; however, some plants also possess these precursors, though at relatively low levels compared with animal-source food products. Various medications have been developed to treat CVD through the gut-microbiota–circulation axis, and they exhibit potent effects in CVD treatment. Nevertheless, such medicines are still being improved, and there are many research gaps that need to be addressed. Furthermore, some medications have unpleasant or adverse effects. Numerous foods and herbs impart beneficial effects upon health and disease. In the past decade, many studies have focused on treating and preventing CVD by modulating the gut microbiota and their metabolites. This review provides an overview of the available information, summarizes current research related to the gut-microbiota–heart axis, enumerates the foods and herbs that are CVD-risk precursors, and illustrates how metabolites become CVD risk factors through the metabolism of gut microbiota. Moreover, we present perspectives on the application of foods and herbs—including prebiotics, probiotics, synbiotics, postbiotics, and antibiotic-like substances—as CVD prevention agents to modulate gut microbiota by inhibiting gut-derived CVD risk factors. Taxonomy (classification by EVISE) Cardiovascular disease, gut microbiota, herbal medicine, preventive medicine, dietary therapy, nutrition supplements.

In this recent publication review the authors aimed to collect evidence of impact of nonsynonymous single nucleotide polymorphisms (nsSNP) in the renin–angiotensin–aldosterone system on patients’ phenotype not only regarding arterial hypertension and its complications, but also the impact on other diseases of interest outside the field of cardiovascular medicine. PubMed database records published between 2017–2020 were searched and all positive case-control studies or positive studies with human DNA were selected. The search identified 104 articles, of which 22 were included on the basis of the inclusion criteria. This paper presents the impact of 44 nsSNPs in panels for genes of renin, angiotensinogen, angiotensin-converting enzyme, angiotensin receptor and aldosterone on the clinical picture of investigated cohorts or on the peptide-protein interactions as consequence of nsSNPs. Genetic variability in nsSNPs of the RAAS is involved in the pathogenesis of arterial hypertension and its complications, and surprisingly also in the pathogenesis of conditions not associated with elevated blood pressure, like neoplasms or inflammatory diseases.

The natural lifespan of the ovary is occasionally interrupted by pathological processes; some are known, but many are unknown. Premature ovarian insufficiency (POI) can be a devastating diagnosis for an adolescent or for someone who has yet to start a family. Common causes of POI include genetic and chromosomal defects, autoimmune damage, and cancer treatments. Knowledge of the pathogenesis of this condition and an awareness of contemporary hormone replacement and fertility options are required to design a multidisciplinary therapeutic approach comprising reproductive medicine, endocrinology, clinical psychology, and assisted fertility expertise.

Peripheral T-cell lymphomas are a heterogeneous, and usually aggressive, group of mature T-cell neoplasms with overlapping clinical, morphologic and immunologic features. A large subset of these neoplasms remains unclassifiable with current diagnostic methods ("not otherwise specified"). Genetic profiling and other molecular tools have emerged as widely applied and transformative technologies for discerning the biology of lymphomas and other hematopoietic neoplasms. Although the application of these technologies to peripheral T-cell lymphomas has lagged behind B-cell lymphomas and other cancers, molecular profiling has provided novel prognostic and diagnostic markers as well as an opportunity to understand the biologic mechanisms involved in the pathogenesis of these neoplasms. Some biomarkers are more prevalent in specific T-cell lymphoma subsets and are being used currently in the diagnosis and/or risk stratification of patients with peripheral T-cell lymphomas. Other biomarkers, while promising, need to be validated in larger clinical studies. In this review, we present a summary of our current understanding of the molecular profiles of the major types of peripheral T-cell lymphoma. We particularly focus on the use of biomarkers, including those that can be detected by conventional immunohistochemical studies and those that contribute to the diagnosis, classification, or risk stratification of these neoplasms.

Drug-induced liver injury (DILI) is an important but rare adverse event which can range from mild liver enzyme elevations to liver failure, transplantation or death. A large proportion of commonly used medications, in addition to herbal and dietary supplements, can cause liver injury. DILI has been categorized as direct or idiosyncratic but indirect liver injury has emerged as a third type of drug-induced liver injury. These types of liver injury may warrant different clinical approach and treatment. Associations of HLA genotypes and risk of DILI have highlighted the importance of the immune system in the pathogenesis of DILI. Furthermore, novel agents affecting the immune response can lead to liver injury, often associated with autoimmune features in serologic tests and liver biopsies. Overall, the diagnosis of DILI remains a challenge as it is requires detailed case evaluation in addition to reviewing the hepatotoxic potentials and clinical signatures of the implicated agents. Biochemical profiles vary between agents and although individual drugs tend to portray a consistent clinicopathologic signature, many drugs have multiple signatures. Thanks to multicenter prospective studies on DILI and websites in the public domain such as LiverTox, physicians are provided with tools to investigate suspected DILI cases to increase the likelihood of establishing adiagnosis. The pathogenesis of DILI, epidemiology and current challenges in the diagnosis and management of the disease are reviewed in the paper.

Background: Circular RNAs (circRNAs) have been identified to be involved in a variety of human diseases such as cancers, cardiovascular diseases, and autoimmune diseases. In recent years, the role of circRNAs in the development of kidney diseases in nephrology has been gradually recognized. Objective: We updated and described the current status of circRNAs in kidney diseases in nephrology. We particularly focused on the roles and mechanisms of circRNAs in systemic lupus erythematosus and lupus nephritis. Methods: We summarized recent reports published on PubMed, Web of Science, Scopus, Scielo databases using keywords circRNAs, kidney diseases or renal diseases, or systemic lupus erythematosus. Results: Studies of circRNAs in certain kidney diseases, such as acute kidney injury, focal segmental glomerulosclerosis, idiopathic membranous nephropathy, IgA nephropathy, diabetic nephropathy, hypertensive renal damage, and particular lupus nephritis address the function and pathogenesis of circRNAs. Mechanisms of circRNAs in the above human kidney diseases so far have focused on the role of sponging microRNAs and regulating the expression of target genes. Moreover, circRNAs have been detected in blood, urine, and kidney tissue samples. These results suggest that circRNAs can serve as biomarkers for the diagnosis and monitoring of the progression of kidney diseases. Conclusion: CircRNAs play important roles in the pathogenesis, diagnosis, and treatment of kidney diseases emphasizing lupus nephritis in nephrology.

The average age for pubertal onset in girls has declined over recent decades. Epidemiological studies in humans and experimental studies in animals suggest a causal role for endocrine disrupting chemicals (EDCs) that are present in our environment. Of concern, current testing and screening regimens are inadequate in identifying EDCs that may affect pubertal maturation, not least because they do not consider early-life exposure. Also, the causal relationship between EDC exposure and pubertal timing is still a matter of debate. To address this issue, we have used current knowledge to elaborate a network of putative adverse outcome pathways (pAOPs) to identify how chemicals can affect pubertal onset. By using the AOP framework, we highlight current gaps in mechanistic understanding that need to be addressed and simultaneously point towards events causative of pubertal disturbance that could be exploited for alternative test methods. We propose 6 pAOPs that could explain the disruption of pubertal timing by interfering with the central hypothalamic trigger of puberty, GnRH neurons, and by so doing highlight specific modes of action that could be targeted for alternative test method development.

This article reviews the current epidemiology of central nervous system tumors. Population-level basic epidemiology, nationally and internationally, and current understanding of germline genetic risk are discussed, with a focus on known and well-studied risk factors related to the etiology of central nervous system tumors.

Целью работы были изучение и оценка эффективности и переносимости препарата Капикор (комбинация γ-бутиробетаина 60 мг и мельдония дигидрата 180 мг), капсулы, производства АО «Олайнфарм» (Латвия) в комплексном лечении пациентов с болезнью Паркинсона и исследование механизма действия Капикора на ротеноновой модели паркинсоноподобного синдрома. Комплексные клинико-нейрофизиологические исследования проведены среди 22 больных болезнью Паркинсона среднего и пожилого возраста (продолжительность болезни 10,40 ± 4,55 года, стадия 2.0–3.0 по Hoehn-Yahr). Экспериментальные исследования проведены на 20 половозрелых крысах-самцах линии Вистар, у которых с помощью ротенона (п/к введение, ежедневно в течение 2 недель в дозе 0,3 мг/100 г массы тела) моделировали паркинсонический синдром. Применение препарата Капикор у больных болезнью Паркинсона способствует снижению выраженности оксидативного стресса — ключевого механизма развития заболевания, уменьшению степени эндотелиальной дисфункции, что дает основание рекомендовать Капикор как эндотелийстабилизирующий препарат в фармакотерапии нейродегенеративного процесса на всех стадиях клинического течения заболевания.

There are multiple syndromes associated with tumors of the central nervous system (CNS). The most common CNS tumor syndrome is neurofibromatosis-1, with well-defined major and minor criteria needed for diagnosis. Other syndromes with variable degree of CNS and extra-CNS involvement that the neurosurgeon should be aware of include neurofibromatosis-2; Turcot syndrome; Cowden syndrome; Gorlin syndrome; Li-Fraumeni syndrome; ataxia-telangiectasia; multiple endocrine neoplasia type 1; von Hippel-Lindau syndrome; and tuberous sclerosis complex. Although most CNS tumor syndromes follow an autosomal dominant pattern of inheritance, the genetic underpinnings of each disease are complex and increasingly better understood.

Tumours of uncertain differentiation represent a markedly heterogeneous group of neoplasms that show no identifiable line of differentiation by currently available technologies, and do not resemble any specific normal cells or tissues. Continuing advances in molecular genetics have significantly aided to our understanding of these tumours, enabling refinements in classification and better insights into their biology, and furthering the development of ancillary immunohistochemical and molecular diagnostic tests and targeted therapies in the clinical setting. This review summarizes key genetic, morphologic and immunohistochemical features for a selection of cutaneous neoplasms of uncertain differentiation, with emphasis on new entities and developments in the diagnostic setting.

Aging is frequently accompanied by various types of physiological deterioration, which increases the risk of human pathologies. Global public health efforts to increase human lifespan has been increasingly focusing on lowering the risk of incidences of aging-related disease, such as diabetes, neurodegenerative diseases, cardiovascular disease and cancers. Dietary interventions is a promising approach to maintain human health during aging. Lactoferrin (LF) is known for its physiologically pleiotropic properties. Anti-aging interventions of LF have proven to be safe and effective for various pharmacological activities such as antioxidants, anti-cellular senescence, anti-inflammation, and anti-carcinogenic. As well as the pivotal role of LF on the modulating of major signaling pathways that influence longevity of organisms. Thus, LF is expected to be able to attenuate the process of aging and greatly ameliorate its effects.

The slowdown, inhibition, or reversal of age-related decline (as a composite of disease, dysfunction, and, ultimately, death) by diet or natural compounds can be defined as dietary geroprotection. While there is no single reliable biomarker to judge the effects of dietary geroprotection, biomarker signatures based on omics (epigenetics, gene expression, microbiome composition) are promising candidates. Recently, omic biomarkers started to supplement established clinical ones such as lipid profiles and inflammatory cytokines. In this review, we focus on human data. We first summarize the current take on genetic biomarkers based on epidemiological studies. However, most of the remaining biomarkers that we describe, whether omics-based or clinical, are related to intervention studies. Then, because of their promising potential in the context of dietary geroprotection, we focus on the effects of berry-based interventions, which up to now have been mostly described employing clinical markers. We provide an aggregation and tabulation of all the recent systematic reviews and meta-analyses that we could find related to this topic. Finally, we present evidence for the importance of the "nutribiography," that is, the influence that an individual's history of diet and natural compound consumption can have on the effects of dietary geroprotection.

Досягнення цільових значень глікемічного профілю — основна мета терапії цукрового діабету (ЦД) 2-го типу. Раннє призначення інсуліну дозволяє не тільки швидко й ефективно знизити показники глікемії й компенсувати вуглеводний обмін, а й зменшити ризик розвитку серцево-судинних ускладнень. Раннє й обґрунтоване використання інсуліну, своєчасна титрація його дози — визначальні фактори досягнення цільових рівнів глікемії у хворих на ЦД 2-го типу, що відкривають широкі можливості досягнення основних цілей лікування ЦД — підтримання довгострокового метаболічного контролю і запобігання судинним ускладненням або відстрочення їх розвитку.

This review comprehensively summarizes epidemiologic evidence of COVID-19 in patients with Type 2 diabetes, explores pathophysiological mechanisms, and integrates recommendations and guidelines for patient management. We found that diabetes was a risk factor for diagnosed infection and poor prognosis of COVID-19. Patients with diabetes may be more susceptible to adverse outcomes associated with SARS-CoV-2 infection due to impaired immune function and possible upregulation of enzymes that mediate viral invasion. The chronic inflammation caused by diabetes, coupled with the acute inflammatory reaction caused by SARS-CoV-2, results in a propensity for inflammatory storm. Patients with diabetes should be aware of their increased risk for COVID-19.

Objective: The molecular mechanisms of bladder cancer development and progression are not clear. Bladder cancer is an important focus for epidemiological studies and understanding clinical implications. Goal: The primary aim of prevention is achieved by limiting exposure to non-genetic risk factors such as smoking, diet, arsenic in drinking water, or aromatic amines at work or elsewhere. Current therapies for bladder cancer are affected by tumor morphology and associated acquired genetic mutations. Methods: A literature search was performed using PubMed, Scopus, ResearchGate, Google, MEDLINE, and ScienceDirect databases to find studies of bladder cancer published between 1984 and early 2020. The focus was articles that address epidemiological risk factors and underlying pathophysiological mechanism. Articles were selected that enabled our review of these factors as well as molecular and structural patterns. Results: There are multiple views of bladder cancer. The literature offers a number of novel insights regarding the development and progression of bladder cancer and possible biomarkers that may be useful in clinical and diagnostic practice. Conclusion: There are several molecular pathways associated with bladder cancer that are frequently updated. In addition, genetic subtypes of bladder tumors are not distinguished clearly that requires future more detailed analysis.

Purpose Radiation therapy to the prostate and pelvic lymph nodes (PLNRT) is part of the curative treatment of high-risk prostate cancer. Yet, the broader influence of radiation therapy on patient physiology is poorly understood. We conducted comprehensive global metabolomic profiling of urine, plasma, and stools sampled from patients undergoing PLNRT for high-risk prostate cancer. Methods and Materials Samples were taken from 32 patients at 6 timepoints: baseline, 2 to 3 and 4 to 5 weeks of PLNRT; and 3, 6, and 12 months after PLNRT. We characterized the global metabolome of urine and plasma using 1H nuclear magnetic resonance spectroscopy and ultraperformance liquid chromatography-mass spectrometry, and of stools with nuclear magnetic resonance. Linear mixed-effects modeling was used to investigate metabolic changes between timepoints for each biofluid and assay and determine metabolites of interest. Results Metabolites in urine, plasma and stools changed significantly after PLNRT initiation. Metabolic profiles did not return to baseline up to 1 year post-PLNRT in any biofluid. Molecules associated with cardiovascular risk were increased in plasma. Pre-PLNRT fecal butyrate levels directly associated with increasing gastrointestinal side effects, as did a sharper fall in those levels during and up to 1 year postradiation therapy, mirroring our previous results with metataxonomics. Conclusions We showed for the first time that an overall metabolic effect is observed in patients undergoing PLNRT up to 1 year posttreatment. These metabolic changes may effect on long-term morbidity after treatment, which warrants further investigation.

Background Immune‐based combination therapies have revolutionized the first‐line treatment for advanced non‐small cell lung cancer (NSCLC). However, for the efficacy and safety, the best treatment option is still uncertain. Methods We conducted a Bayesian network meta‐analysis of randomized controlled trials (RCTs) to evaluate first‐line immune‐based combination therapies for advanced NSCLC. Results Fourteen trials involving 8467 patients were included. For the programmed cell death‐ligand 1 (PD‐L1) expression non‐selective patients, there were no significant differences among all the treatment modes for overall survival (OS), but the ranking profiles indicated that Immunotherapy + Immunotherapy + Chemotherapy (IO + IO + Chemo) was most likely to be the best mode (probability = 68%). Immunotherapy + Immunotherapy + Anti‐angiogenic therapy + Chemotherapy (IO + Anti‐angio + Chemo) was significantly better than most other treatment modes for progression‐free survival (PFS) with better objective response rate (ORR) and more obvious grade ≥3 treatment‐related adverse events (TRAEs). In PD‐L1‐high cohort, IO + Anti‐angio + Chemo seemed to be the best mode for OS, PFS, and ORR according to the ranking profiles. In PD‐L1‐intermediate and PD‐L1‐negative cohort, IO + IO + Chemo was inclined to be ranked first for prolonging OS (probability = 78%; 37%) and IO + Anti‐angio + Chemo was most likely to provide best PFS (probability = 96%; 100%). Conclusion IO + IO + Chemo has great potential to improve the OS regardless of histology type, especially in PD‐L1‐intermediate and PD‐L1‐negative cohort. IO + Anti‐angio + Chemo shows great superiority in improving the short‐term survival accompanied by increasing grade ≥3 TRAEs., IO + IO + Chemo has great potential to be recommended to improve OS regardless of the histology type especially in PD‐L1‐intermediate and PD‐L1‐negative cohort. IO + Anti‐angio + Chemo shows great superiority in improving the short‐term survival accompanied by relatively increasing TRAEs. Our findings are of great significance for the first‐line treatment of advanced NSCLC and provide reference for clinicians and patients to achieve precise therapy.

Results of biochemical tests of 172 patient data (among them 84 men data and 88 women data, resp.) before and after administration of statins were studied. All monitored patients are characterized by lipoprotein metabolism failure or other kind of lipidaemia. The calculations were performed using several chemometrical methods pursuing visualization of most important biochemical parameters and classification of the patient blood samples by means of up-to-date software packages. The dependences of the content of most common biochemical parameters upon the treatment of patients by statins were elucidated in detail.

Background Reliable molecular markers are much needed for early prediction of recurrence in muscle‐invasive bladder cancer (MIBC) patients. We aimed to build a long‐noncoding RNA (lncRNA) signature to improve recurrence prediction and lncRNA‐based molecular classification of MIBC. Methods LncRNAs of 320 MIBC patients from the Cancer Genome Atlas (TCGA) database were analyzed, and a nomogram was established. A molecular classification system was created, and immunotherapy and chemotherapy response predictions, immune score analysis, immune infiltration analysis, and mutational data analysis were conducted. Survival analysis validation was also performed. Results An eight‐lncRNA signature classifed the patients into high‐ and low‐risk subgroups, and these groups had significantly different (disease‐free survival) DFS. The ability of the eight‐lncRNA signature to make an accurate prognosis was tested using a validation dataset from our samples. The nomogram achieved a C‐index of 0.719 (95% CI, 0.674–0.764). Time‐dependent receiver operating characteristic curve (ROC) analysis indicated the superior prognostic accuracy of nomograms for DFS prediction (0.76, 95% CI, 0.697–0.807). Further, the four clusters (median DFS = 11.8, 15.3, 17.9, and 18.9 months, respectively) showed a high frequency of TTN (cluster 1), fibroblast growth factor receptor‐3 (cluster 2), TP53 (cluster 3), and TP53 mutations (cluster 4), respectively. They were enriched with M2 macrophages (cluster 1), CD8+ T cells (cluster 2), M0 macrophages (cluster 3), and M0 macrophages (cluster 4), respectively. Clusters 2 and 3 demonstrated potential sensitivity to immunotherapy and insensitivity to chemotherapy, whereas cluster 4 showed potential insensitivity to immunotherapy and sensitivity to chemotherapy. Conclusions The eight‐lncRNA signature risk model may be a reliable prognostic signature for MIBC, which provides new insights into prediction of recurrence of MIBC. The model may help clinical decision and eventually benefit patients., Reliable molecular markers are much needed for early prediction of recurrence in patients with muscle‐invasive bladder cancer (MIBC). It's the first time to build an lncRNA signature to improve recurrence prediction and for lncRNA‐based molecular classification of MIBC, which can be used to guide clinical treatment and provide precision therapy.

Cystinuria is the most common genetic cause of nephrolithiasis in children. It is considered a heritable aminoaciduria as the genetic defect affects the reabsorption of cystine and three other amino acids (ornithine, lysine, and arginine) in the renal proximal tubule. Patients affected by this condition have elevated excretion of cystine in the urine, and because of this amino acid's low solubility at normal urine pH, patients tend to form cystine calculi. To date, two genes have been identified as disease-causative: SLC3A1 and SLC7A9, encoding for the two subunits of the heterodimeric transporter. The clinical features of this condition are solely related to nephrolithiasis. The diagnosis is usually made during infancy or adolescence, but cases of late diagnosis are common. The goal of therapy is to reduce excretion and increase the solubility of cystine, through both modifications of dietary habits and pharmacological treatment. However, therapeutic interventions are not always sufficient, and patients often have to undergo several surgical procedures during their lives to treat recurrent nephrolithiasis. The goal of this literature review is to synthesize the available evidence on diagnosis and management of patients affected by cystinuria in order to provide physicians with a practical tool that can be used in daily clinical practice. This review also aims to shed some light on new therapy directions with the aim of ameliorating kidney outcomes while improving adherence to treatment and quality of life of cystinuric patients.

BACKGROUND Immunosuppression is essential after organ transplantation to prevent severe graft injury due to rejection, but in long-term, transplanted organs are generally accepted with minimal dose of immunosuppression, and adverse effects of it such as renal dysfunction, diabetes and development of malignancies might become to exceed over the benefits in majority of the cases. Accordingly, to achieve the immunologic tolerance has been the ultimate goal in organ transplantation, and the liver has been well recognized as the tolerogenic organ compared to other organs. METHODS We referred the reported studies showing the actual protocol to achieve the immunologic tolerance after clinical liver transplantation. RESULTS Actually, two main procedures as "elective weaning of immunosuppression" and/or "cell therapy" using various immune-related cells have been introduced to induce the immunologic tolerance in clinical liver transplantation. The cell therapy, especially using regulatory T-cell has been reported to achieve definitive immunologic tolerance in living donor liver transplantation. CONCLUSION Although it is still developing, the induction of immunologic tolerance in clinical liver transplantation is realistic. Herein, the current topics of immunologic tolerance in liver transplantation is described.

Purpose of review Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity and has wide ranging extrahepatic manifestations, including through cardiometabolic pathways. As such, there is growing interest in the impact of NAFLD on cerebrovascular disease and brain health more broadly. In this review, we assess recent research into understanding the association between NAFLD and brain health while highlighting potential clinical implications. Recent findings Mechanistically, NAFLD is characterized by both a proinflammatory and proatherogenic state, which results in vascular inflammation and neurodegeneration, potentially leading to clinical and subclinical cerebrovascular disease. Mounting epidemiological evidence suggests an association between NAFLD and an increased risk and severity of stroke, independent of other vascular risk factors. Studies also implicate NAFLD in subclinical cerebrovascular disease, such as carotid atherosclerosis and microvascular disease. In contrast, there does not appear to be an independent association between NAFLD and cognitive impairment. Summary The current literature supports the formulation of NAFLD as a multisystem disease that may also have implications for cerebrovascular disease and brain health. Further prospective studies are needed to better assess a temporal relationship between the two diseases, confirm these early findings, and decipher mechanistic links.

The therapeutic landscape for cardiac amyloidosis is rapidly evolving. In the last decade, our focus has shifted from dealing with the inevitable complications of continued extracellular infiltration of amyloid fibrils to earlier identification of these patients with prompt initiation of targeted therapy to prevent further deposition. Although much of the focus on novel targeted therapies is within the realm of transthyretin amyloidosis, light chain amyloidosis has benefited due to an overlap particularly in the final common pathway of fibrillogenesis and extraction of amyloid fibrils from the heart. Here, we review the targeted therapeutics for transthyretin and light chain amyloidosis. For transthyretin amyloidosis, the list of current and future therapeutics continues to evolve; and therefore, it is crucial to become familiar with the underlying mechanistic pathways of the disease. Although targeted therapeutic choices in AL amyloidosis are largely driven by the hematology team, the cardiac adverse effect profiles of these therapies, particularly in those with advanced amyloidosis, provide an opportunity for early recognition to prevent decompensation and can help inform recommendations regarding therapy changes when required.

Ascorbic acid (vitamin C) is a vital nutrient that belongs to the group of antioxidants. Vitamin C plays an important role in the functioning of the central (CNS) and peripheral nervous system (PNS), including maturation and differentiation of neurons, formation of myelin, synthesis of catecholamines, modulation of neurotransmission and antioxidant protection. Neurological diseases and mental disorders are characterized by increased generation of free radicals. At the same time, the highest concentrations of vitamin C are found in the brain and neuroendocrine tissues. It is believed that vitamin C can affect the age of debut and the course of many neurological diseases and mental disorders. However, its potential therapeutic role continues to be studied. The efficacy and safety of vitamin C is likely influenced by the pharmacogenetic profile of the patient, including the carriage of single-nucleotide variants (SNVS), candidate genes associated with vitamin C metabolism in the human body in normal and neuropsychic disorders. The purpose of this thematic review is to update current knowledge about the role of vitamin C pharmacogenetics in the efficacy and safety of its use in neurological diseases (amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Huntington's disease, Alzheimer's disease, etc.) and mental disorders (depression, anxiety, schizophrenia, etc.). Special attention is paid to the possibility of translating the results of pharmacogenetic studies into real clinical practice in neurology and psychiatry.

Barth Syndrome is an X-linked disorder of mitochondrial cardiolipin metabolism caused by pathogenic variants in TAFAZZIN with pleiotropic effects including cardiomyopathy, neutropenia, growth delay, and skeletal myopathy. Management requires a multidisciplinary approach to the organ-specific manifestations including specialists from cardiology, hematology, nutrition, physical therapy, genetics, and metabolism. Currently, treatment is centered on management of specific clinical features, and is not targeted towards remediating the underlying biochemical defect. However, two clinical trials have been recently undertaken which target the mitochondrial pathology of this disease: a study to examine the effects of elamipretide, a cardiolipin targeted agent, and a study to examine the effects of bezafibrate, a peroxisome proliferator-activated receptor (PPAR) agonist. Treatments to directly target the defective TAFAZZIN pathway are under development, including enzyme and gene therapies. This article is protected by copyright. All rights reserved.

Muscular dystrophies encompass a wide and heterogeneous subset of hereditary myopathies that manifest by the structural or functional abnormalities in the skeletal muscle. Some pathogenic mutations induce a dysfunction or loss of proteins that are critical for the stability of muscle cells, leading to progressive muscle degradation and weakening. Several studies have well-established cognitive deficits in muscular dystrophies which are mainly due to the disruption of brain-specific expression of affected muscle proteins. We provide a comprehensive overview of the types of muscular dystrophies that are accompanied by intellectual disability by detailed consulting of the main libraries. The current paper focuses on the clinical and molecular evidence about Duchenne, congenital, limb-girdle, and facioscapulohumeral muscular dystrophies as well as myotonic dystrophies. Because these syndromes impose a heavy burden of psychological and financial problems on patients, their families, and the health care community, a thorough examination is necessary to perform timely psychological and medical interventions and thus improve the quality of life.

Anorexia nervosa (AN), an eating disorder, is characterized by extreme weight loss and fear of weight gain. Psychosocial factors are thought to play important roles in the development and progression of AN; however, biological factors also presumably contribute to eating disorders. Recent evidence has shown that the gut microbiota plays an important role in pathogenesis of neuropsychiatric disorders including AN. In this article, we describe the possible role of the gut microbiota in the development and persistence of AN, based on the latest research works, including those of our group.

Cancer of unknown primary (CUP) refers to metastatic tumors for which the primary tumor of origin cannot be determined at the time of diagnosis, despite extensive clinicopathologic investigations. Molecular profiling is increasingly able to predict a probable primary tumor type for CUP when clinicopathologic workup is inconclusive. Numerous studies have explored the use of various molecular profiling techniques for identification of site/tissue of origin of CUP. These techniques include gene expression profiling utilizing microarray, reverse transcriptase polymerase chain reaction, RNA-sequencing, somatic gene mutation profiling with next-generation DNA sequencing, and epigenomics including DNA methylation profiling. Despite the generally poor prognosis of CUP, a minority of patients can expect to benefit from targeted therapy despite being agnostic to the tissue of origin. Studies have explored the use of various molecular profiling techniques to predict prognostic and therapeutic biomarkers, with the goal of improving outcome for patients with CUP. However, discordant results between non-randomized and randomized clinical trials in evaluating tumor-type specific therapies raise uncertainties of the benefits of molecularly-predicted tissue of origin-based treatment in routine clinical use. Nevertheless, the current overall trend is in favor of using molecular tools to refine the diagnosis and clinical management of patients with CUP. More large-cohort, randomized prospective studies are needed to assess and validate the utility and feasibility of molecular profiling to uncover potentially targetable genetic alterations. These efforts will also yield further biological insights into the biology and pathogenesis of CUP (Graphical Abstract).

Background Rapid on‐site cytologic evaluation (ROSE) helps to improve the diagnostic accuracy in endobronchial ultrasound (EBUS) procedures. However, cytologists are seldom available to perform ROSE in many institutions. Recent studies have investigated the application of deep learning in cytologic image analysis. As such, the present study analyzed lung cytologic images obtained by EBUS procedures, and employed deep‐learning methods to distinguish between benign and malignant cells and to semantically segment malignant cells. Methods Ninety‐seven patients who underwent 104 EBUS procedures were enrolled. Four hundred and ninety‐nine lung cytologic images obtained via ROSE, including 425 malignant and 74 benign, and most malignant were lung adenocarcinoma (64.3%). All the images were used to train a residual network model with 101 layers (ResNet101), with suitable hyperparameters selected to classify benign and malignant lung cytologic images. An HRNet model was also employed to mark the area of malignant cells. Automatic patch‐cropping was adopted to facilitate dataset preparation. Results Malignant cells were successfully classified by ResNet101 with 98.8% classification accuracy, 98.8% sensitivity, and 98.8% specificity in patch‐based classification; 95.5% classification accuracy in image‐based classification; and 92.9% classification accuracy in patient‐based classification. Malignant cell area was successfully marked by HRNet with a mean intersection over union of 89.2%. The automatic cropping method enabled the system to complete diagnosis within 1 s. Conclusions This is the first study to combine lung cytologic image deep‐learning classification with semantic segmentation. The model was optimized for high accuracy and the automatic cropping facilitates the clinical application of our model. The success in both lung cytologic images classification and semantic segmentation on our dataset shows a promising result for clinical application in the future., This study leveraged the high computational speed characteristics of deep learning to distinguish and segmentally mark malignant cells in lung cytologic images obtained by EBUS procedures. Classification with ResNet101 and segmentation with HRNet were completed within 1 s and with high accuracy.

The cornerstone of management in patients with acute promyelocytic leukemia (APL) is early diagnosis and prompt initiation of treatment with an all-trans retinoic acid (ATRA)-based regimen. Identification of the t(15;17)(PML-RARA) chromosomal translocation through conventional cytogenetics fluorescence in-situ hybridization (FISH) or detection of the promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα) fusion through RT-PCR represent the current standard of care for diagnosing APL. However, about 1–2% of patients with APL have a variant translocation involving other fusion partners with RARα besides PML. These patients present a unique diagnostic and clinical challenge in that conventional cytogenetics in addition to FISH and/or RT-PCR for PML-RARα may fail to identify these clinically relevant genetic lesions leading to an inappropriate diagnosis and treatment. We present two cases of patients who had APL with variant translocations whose bone marrow specimens were sent to the University of Michigan for enrollment in the MI-ONCOSEQ study (HUM00067928) after standard testing failed to identify PML-RARα or t(15;17) despite a phenotypic concern for this diagnosis. In these two patients, whole exome and transcriptome profiling via the MI-ONCOSEQ platform identified a PRKAR1A-RARα fusion in one patient and ZBTB16-RARα fusion in another patient. These cases illustrate the utility of whole exome and transcriptome profiling in diagnosing variant translocations in patients in whom there is a high clinical suspicion for APL based on hematopathology review.

Background Alzheimer’s disease (AD), cardiovascular disease (CVD), and diabetes are some of the most common causes of morbidity and mortality among the aging populations and cause a heavy burden on the worldwide healthcare system. In this review, we briefly highlighted cellular inflammation-based pathways of diabetes mellitus and CVD through receptor for advanced glycation end products AGEs or RAGE leading to Alzheimer’s disease and interrelation between these vascular and metabolic disorders. The articles were retrieved from Google Scholar, Science Direct, and PubMed databases using the following terms: Alzheimer’s; AGEs; RAGE; RAGE in Alzheimer’s; AGEs in Alzheimer’s; RAGE in diabetes; RAGE related pathways of CVD; RAGE in hypertension; RAGE and RAS system; RAGE and oxidative stress. Main body of the abstract AD is a neurodegenerative disease characterized by cognitive dysfunction and neuronal cell death. Vascular complications like hypertension, coronary artery disease, and atherosclerosis as well as metabolic syndromes like obesity and diabetes are related to the pathophysiology of AD. RAGE plays significant role in the onset and progression of AD. Amyloid plaques and neurofibrillary tangles (NFT) are two main markers of AD that regulates via RAGE and other RAGE/ligands interactions which also induces oxidative stress and a cascade of other cellular inflammation pathways leading to AD. Though AD and diabetes are two different disorders but may be inter-linked by AGEs and RAGE. In long-term hyperglycemia, upregulated AGEs interacts with RAGE and produces reactive oxygen species which induces further inflammation and vascular complications. Aging, hypercholesterolemia, atherosclerosis, hypertension, obesity, and inflammation are some of the main risk factors for both diabetes and dementia. Chronic hypertension and coronary artery disease disrupt the functions of the blood-brain barrier and are responsible for the accumulation of senile plaques and NFTs. Short conclusion RAGE plays a role in the etiology of Aβ and tau hyperphosphorylation, both of which contribute to cognitive impairment. So far, targeting RAGE may provide a potential sight to develop therapies against some metabolic disorders.

Background Computed tomography (CT)‐detected extramural venous invasion (EMVI) has been identified as an independent factor that can be used for risk stratification and prediction of prognosis in patients with gastric cancer (GC). Overall survival (OS) is identified as the most important prognostic indicator for GC patients. However, the molecular mechanism of EMVI development and its potential relationship with OS in GC are not fully understood. In this radiogenomics‐based study, we sought to investigate the molecular mechanism underlying CT‐detected EMVI in patients with GC, and aimed to construct a genomic signature based on EMVI‐related genes with the goal of using this signature to predict the OS. Materials and Methods Whole mRNA genome sequencing of frozen tumor samples from 13 locally advanced GC patients was performed to identify EMVI‐related genes. EMVI‐prognostic hub genes were selected based on overlapping EMVI‐related differentially expressed genes and OS‐related genes, using a training cohort of 176 GC patients who were included in The Cancer Genome Atlas database. Another 174 GC patients from this database comprised the external validation cohort. A risk stratification model using a seven‐gene signature was constructed through the use of a least absolute shrinkage and selection operator Cox regression model. Results Patients with high risk score showed significantly reduced OS (training cohort, p = 1.143e‐04; validation cohort, p = 2.429e‐02). Risk score was an independent predictor of OS in multivariate Cox regression analyses (training cohort, HR = 2.758; 95% CI: 1.825–4.169; validation cohort, HR = 2.173; 95% CI: 1.347–3.505; p, Imaging feature of computed tomography‐detected extramural venous invasion (EMVI) has been identified as an independent risk factor of gastric cancer (GC). We aimed to investigate the molecular mechanism of EMVI based on whole mRNA genome sequencing of frozen cancerous samples from 13 locally advanced GC. Then using TCGA database, we constructed an EMVI‐related gene model and found it could predict the prognosis in patients with GC.

Hearing loss (HL) is one of the most common sensory impairments worldwide and represents a critical medical and public health issue. Since the mid-1900s, great efforts have been aimed at understanding the etiology of both syndromic and non-syndromic HL and identifying correlations with specific audiological phenotypes. The extraordinary discoveries in the field of molecular genetics during the last three decades have contributed substantially to the current knowledge. Next-generation sequencing technologies have dramatically increased the diagnostic rate for genetic HL, enabling the detection of novel variants in known deafness-related genes and the discovery of new genes implicated in hearing disease. Overall, genetic factors account for at least 40% of the cases with HL, but a portion of affected patients still lack a definite molecular diagnosis. Important steps forward have been made, but many aspects still have to be clarified. In particular, the role of epigenetics in the development, function and pathology of hearing is a research field that still needs to be explored. This research is extremely challenging due to the time- and tissue-dependent variability of the epigenetic changes. Multisystem diseases are expected to be investigated at first: specific epi-signatures have been identified for several syndromic disorders and represent potential markers for molecular diagnostics.

Background Patients with 21-hydroxylase deficiency congenital adrenal hyperplasia (21OHD-CAH) have poor health outcomes with increased mortality, short stature, impaired fertility, and increased cardiovascular risk factors such as obesity. To address this, there are therapies in development that target the clinical goal of treatment, which is to control excess androgens with an adrenal replacement dose of glucocorticoid. Methods Narrative review of publications on recent clinical developments in the pharmacotherapy of congenital adrenal hyperplasia. Summary Therapies in clinical development target different levels of the hypothalamo–pituitary–adrenal axis. Two corticotrophin-releasing factor type 1 (CRF1) receptor antagonists, Crinecerfont and Tildacerfont, have been trialled in poorly controlled 21OHD-CAH patients, and both reduced ACTH and androgen biomarkers while patients were on stable glucocorticoid replacement. Improvements in glucocorticoid replacement include replacing the circadian rhythm of cortisol that has been trialled with continuous s.c. infusion of hydrocortisone and Chronocort, a delayed-release hydrocortisone formulation. Chronocort optimally controlled 21OHD-CAH in 80% of patients on an adrenal replacement dose of hydrocortisone, which was associated with patient-reported benefits including restoration of menses and pregnancies. Adrenal-targeted therapies include the steroidogenesis-blocking drug Abiraterone acetate, which reduced adrenal androgen biomarkers in poorly controlled patients. Conclusions CRF1 receptor antagonists hold promise to avoid excess glucocorticoid replacement in patients not controlled on standard or circadian glucocorticoid replacement such as Chronocort. Gene and cell therapies are the only therapeutic approaches that could potentially correct both cortisol deficiency and androgen excess.

Objective Next generation sequencing (NGS) has expanded the diagnostic paradigm turning the focus to the growth plate. The aim of the study was to determine the prevalence of variants in genes implicated in skeletal dysplasias in probands with short stature and mild skeletal anomalies. Design Clinical and radiological data were collected from 108 probands with short stature and mild skeletal anomalies. Methods A customized skeletal dysplasia NGS panel was performed. Variants were classified using ACMG recommendations and Sherloc. Anthropometric measurements and skeletal anomalies were subsequently compared in those with or without an identified genetic defect. Results Heterozygous variants were identified in 21/108 probands (19.4%). Variants were most frequently identified in ACAN (n = 10) and IHH (n = 7) whilst one variant was detected in COL2A1, CREBBP, EXT1, and PTPN11. Statistically significant differences (P < 0.05) were observed for sitting height/height (SH/H) ratio, SH/H ratio standard deviation score (SDS), and the SH/H ratio SDS >1 in those with an identified variant compared to those without. Conclusions A molecular defect was elucidated in a fifth of patients. Thus, the prevalence of mild forms of skeletal dysplasias is relatively high in individuals with short stature and mild skeletal anomalies, with variants in ACAN and IHH accounting for 81% of the cases. An elevated SH/H ratio appears to be associated with a greater probability in detecting a variant, but no other clinical or radiological feature has been found determinant to finding a genetic cause. Currently, we cannot perform extensive molecular studies in all short stature individuals so detailed clinical and radiological phenotyping may orientate which are the candidate patients to obtain worthwhile results. In addition, detailed phenotyping of probands and family members will often aid variant classification.

Background Ovarian cancer (OC) is the most lethal gynecological malignancy. The objective of this study was to establish and validate an individual aging‐related gene signature and a clinical nomogram that can powerfully predict independently the overall survival rate of patients with ovarian cancer. Methods Data on transcriptomic profile and relevant clinical information were retrieved from The Cancer Genome Atlas (TCGA) database as a training group, and the same data from three public Gene Expression Omnibus (GEO) databases as validation groups. Univariate Cox regression analysis, lasso regression analysis, and multiple multivariate Cox analysis were analyzed sequentially to select the genes to be included in the aging‐associated signature. A risk scoring model was established and verified, the predictive value of the model was evaluated, and a clinical nomogram was established. Results We found eight genes that were most relevant to prognosis and constructed an eight‐mRNA signature. Based on the model, each OC patient's risk score was able to be calculated and patients were split into groups of low and high risks with a distinct outcome. Survival analysis confirmed that the outcome of patients in the high‐risk group was dramatically shorter than that of those in the low‐risk group, and the eight‐mRNA signature can be considered as a powerful and independent predictor that could predict the outcome of OC patient. Additionally, the risk score and age can be used to construct a clinical nomogram as a simpler tool for predicting prognosis. We also explored the association between the risk score and immunity and drug sensitivity. Conclusion This study suggested that the aging‐related gene signature could be used as an intervention point and latent prognostic predictor in OC, which may provide new perceptions for postoperative treatment strategies., We constructed a prognostic signature of eight aging‐related genes and a clinical nomogram that provides potential biomarkers for predicting the prognosis of patients with OC, helps to understand the potential pathogenesis of OC, and can possibly be used to develop new approaches for the clinical treatment of ovarian cancer.

Background The majority of patients with small‐cell lung cancer (SCLC) show a good response in the early stages of treatment, but more than 90% of patients will develop drug resistance. Therefore, biomarkers are urgently needed to identify patients who can benefit from systemic treatment. Methods We prospectively enrolled 52 extensive‐stage SCLC patients before treatment from a local hospital to identify mutations related to patient prognosis, and verified them in the published Jiang's cohort and George's cohort. Results We found that patients with high mutations (mut‐high) in the fatty acid (FA) metabolism pathway had a longer progression‐free survival (PFS) in the local hospital cohort (HR = 0.446, 95% CI, 0.207–0.959, p = 0.0387) and a longer overall survival (OS) in Jiang's cohort (HR = 0.549, 95% CI, 0.314–0.960, p = 0.0351) than patients with low mutations (mut‐low). Multivariate analysis suggested that mut‐high status was an independent prognostic factor in both cohorts. George's cohort verified that mut‐high status was associated with a longer OS than mut‐low status (HR = 0.730, 95% CI 0.440–1.220, p = 0.2277). The possible mechanisms were as follows: the frequency of mutated FA synthase (FASN) in the mut‐high group was greater than that in the mut‐low group, and pathways related to the cell cycle, DNA repair, and oxidative phosphorylation were enriched in the mut‐high group. Conclusions The prognosis of SCLC patients treated with chemotherapy was better among patients with more mutations in the FA metabolism pathway, and the underlying mechanisms could be found at the genome and transcriptome levels., We prospectively enrolled 52 extensive‐stage SCLC patients before treatment from local hospital to identify mutations related to patient prognosis. We found that the patients with high mutations (mut‐high) in the fatty acid (FA) metabolism pathway had better prognosis in the local hospital cohort and the Jiang's cohort than patients with low mutations (mut‐low). Then it was verified in George's cohort that mut‐high status was associated with a longer OS than mut‐low status. Finally, the possible mechanisms were explored from the genome and transcriptome levels.

Following severe injury, biomineralization is disrupted and limited therapeutic options exist to correct these pathologic changes. This study utilized a clinically relevant murine model of polytrauma including a severe injury with concomitant musculoskeletal injuries to identify when bisphosphonate administration can prevent the paradoxical decrease of biomineralization in bone and increased biomineralization in soft tissues, yet not interfere with musculoskeletal repair. Systemic and intrinsic mechanisms in bone and soft tissues help promote biomineralization to the skeleton, while preventing it in soft tissues. However, severe injury can disrupt this homeostatic biomineralization tropism, leading to adverse patient outcomes due to a paradoxical decrease of biomineralization in bone and increased biomineralization in soft tissues. There remains a need for therapeutics that restore the natural tropism of biomineralization in severely injured patients. Bisphosphonates can elicit potent effects on biomineralization, though with variable impact on musculoskeletal repair. Thus, a critical clinical question remains as to the optimal time to initiate bisphosphonate therapy in patients following a polytrauma, in which bone and muscle are injured in combination with a severe injury, such as a burn. To test the hypothesis that the dichotomous effects of bisphosphonates are dependent upon the time of administration relative to the ongoing biomineralization in reparative bone and soft tissues, this study utilized murine models of isolated injury or polytrauma with a severe injury, in conjunction with sensitive, longitudinal measure of musculoskeletal repair. This study demonstrated that if administered at the time of injury, bisphosphonates prevented severe injury-induced bone loss and soft tissue calcification, but did not interfere with bone repair or remodeling. However, if administered between 7 and 21 days post-injury, bisphosphonates temporally and spatially localized to sites of active biomineralization, leading to impaired fracture callus remodeling and permanence of soft tissue calcification. There is a specific pharmacologic window following polytrauma that bisphosphonates can prevent the consequences of dysregulated biomineralization, yet not impair musculoskeletal regeneration.

Irradiation of platelet products is generally used to prevent transfusion-associated graft-versus-host disease (TA-GvHD) as well as transfusion-transmitted infections. As an essential prerequisite, gamma-irradiation of blood products prior to transfusion is required in patients who may develop TA-GVHD. Most studies suggest that gamma irradiation has no significant effect on the quality of platelet products; however, more recent studies have shown that the oxidative effects of gamma irradiation can lead to the induction of platelet storage lesion (PSL) and to some extent reduce the efficiency of transfused platelets. As the second widely used irradiation technique, UV-illumination was primarily introduced to reduce the growth of infectious agents during platelet storage, with the advantage that this method can also prevent TA-GvHD. However, the induction of oxidative conditions and platelet pre-activation that lead to PSL is more pronounced after UV-based methods of pathogen reduction. Since these lesions are large enough to clearly affect the post-transfusion platelet recovery and survival, more studies are needed to improve the safety and effectiveness of pathogen reduction technologies (PRTs). Therefore, pointing to other benefits of PRTs, such as preventing TA-GvHD or prolonging the shelf life of products by eliminating the possibility of pathogen growth during storage, does not yet seem to justify their widespread use due to above-mentioned effects. Even for gamma-irradiated platelets, some researchers have suggested that due to decreased 1-hour post-transfusion increments and increased risk of platelet refractoriness, their use should be limited to the patients who may develop TA-GVHD. It is noteworthy that due to the effect of X-rays in preventing TA-GvHD, some recent studies are underway to examine its effects on the quality and effectiveness of platelet products and determine whether X-rays can be used as a more appropriate and cost-effective alternative to gamma radiation. The review presented here provides a detailed description about irradiation-based technologies for platelet products, including their applications, mechanistic features, advantages, and disadvantages.

Background Some significant differences exist between the outcomes of left‐ and right‐sided colon cancer patients. The presence of nodal metastases is a critical prognostic factor, especially in the absence of distant metastasis. Our research studied the lymph nodes status of left‐ and right‐sided colon cancer patients to determine the influence of this factor on prognosis. Methods Our data were obtained from the Surveillance, Epidemiology and End Results (SEER) database. We used the chi‐square test to analyze the clinicopathological characteristics. The X‐tile program was adopted to acquire optimal cutoff points of lymph node index. Kaplan–Meier curves were used to analyze prognosis and multivariate Cox regression models were performed to identify the independent factors associated with survival. Nomograms were built to predict the overall survival of patients, Harrell's C‐index and calibration plots were used to validate the nomograms. Results The study included 189,941 patients with colon cancer without metastasis (left 69,885, right 120,056) between 2004 and 2015. There are more patients with adequate examined lymph nodes in right‐sided. Lymph node status in patients with right colon cancer has a more significant impact on the risk of death. LODDS (C‐index: 0.583; AIC: 6875.4) was used to assess lymph node status. The nomograms showed that lymph node status was the main factor to predict the outcome in right‐sided colon patients. Conclusions The influence of lymph node status on predicting prognosis is significantly different between patients with left and right colon cancer without metastasis. The tumor site needs to be considered when lymph node status is used to assess the outcome of patients., The effect of lymph node status on predicting prognosis differed significantly between left‐sided and right‐sided colon cancer patients. The tumor site needs to be considered when lymph node status is used to assess the outcome of patients.

End-stage liver diseases have long been a threat to human health, and so far, the treatment of these diseases lacks effective means. Allogenic organ transplantation has become the last straw for most of the patients with end-stage liver diseases. However, this technique has been greatly limited by the serious shortage of donors and other factors, such as immune rejection, drug syndrome, and high cost. Recently, the emergence of three-dimensional (3D) bioprinting technologies, together with the magnetic resonance imaging (MRI) and computed tomography (CT) techniques, has driven the rapid growth of this field toward liver therapies. There are several basic requirements for liver 3D bioprinting. From information collection of diseased livers, to 3D printing of liver substitutes (containing the major structural, material and functional characters), and to clinical applications, suitable ‘bioinks’ and ‘bioprinters’ have played essential roles. In this review, we highlight the advanced ‘bioinks’ and ‘bioprinters’ that have been used for vascularized and innervated liver tissue 3D bioprinting. Further studies for the incorporation of biliary networks in the bioartificial livers have been emphasized. It is expected that when all the bottle-neck problems for liver 3D bioprinting are solved, batch (i.e. mass) and personalized production of bioartificial livers will make it very easy to treat end-stage liver diseases.

Polycystic ovary syndrome (PCOS) is one of the most important gynecological disorders of women in the age of reproduction. Different hormonal and inflammatory cross-talks may play in the appearance of its eventual complications as a leading cause of infertility. Excessive production of reactive oxygen species over the power of the antioxidant system as oxidative stress is known to contribute to a variety of diseases like PCOS. Thus, the utilization of antioxidants can be efficient in preventing or assistant in treating these diseases. In this review, we describe the clinical trial studies that have examined the efficiency of antioxidant strategies against PCOS and the possible underlying mechanisms. The investigations presented here lead us to consider that targeting oxidative stress pathways is probably a powerful promising therapeutic approach towards PCOS. There is preparatory evidence of the effectiveness of antioxidant interventions in ameliorating some of the PCOS complications, including metabolic and hormonal disorders. Due to limited data and relatively few clinical trials, many of these interventions need further investigation before they can be considered effective agents for routine clinical use.

Coronavirus disease 2019 (COVID-19), the third type of coronavirus pneumonia after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), is spreading widely worldwide now. This pneumonia causes not only respiratory symptoms but also multiple organ dysfunction, including thrombotic diseases such as ischemic stroke. The purpose of this review is to explore whether COVID-19 is a risk factor for ischemic stroke and its related pathophysiological mechanisms. Based on the high thrombosis rate and frequent strokes of COVID-19 patients, combined with related laboratory indicators and pathological results, the discussion is mainly from two aspects: nerve invasion and endothelial dysfunction. SARS-CoV-2 can directly invade the CNS through blood-borne and neuronal retrograde pathways, causing cerebrovascular diseases. In addition, the endothelial dysfunction in COVID-19 is almost certain. Cytokine storm causes thromboinflammation, and downregulation of ACE2 leads to RAS imbalance, which eventually lead to ischemic stroke.

The spectrum of axial spondyloarthritis (AxSpA) (including both non-radiographic and radiographic AxSpA), also known as ankylosing spondylitis AS, has achieved growing recognition. With the development of treatments not only effective in controlling disease activity but also in slowing radiographic progression, and given the cost and risk profiles of these novel treatments and the limitations of current clinical criteria, imaging and peripheral blood biomarkers (C-reactive protein, HLA-B27 testing), the need for better biomarkers has never been greater. The purpose of this review is to present up-to-date information on the biomarkers for the diagnosis for assessing disease diagnosis, activity, treatment response, and radiographic progression of AxSpA, and entails multiple search strings used to identify articles of interest published in PubMed and the Cochrane database up to May 1, 2021. We present the current status of research in serologic biomarkers such as cytokines, adipokines, matrix metalloproteinases, calprotectin, CD74, antibodies, bone turnover markers, and circulating protein fragments of cartilage and connective tissue degradation and other biomarkers. Despite a great deal of work, most serologic results have been disappointing and to date none perform better than CRP. Recent promising preliminary data for some has been published, but require further confirmation. Transcriptomic biomarkers such as micro-RNAs and genetic biomarkers also show promise to assist in diagnosis and possibly for radiographic severity, including a recently developed panel of genetic risk markers used in a polygenic risk score instrument in AS diagnosis. These need further confirmation and application in AS as well as in nr-AxSpA.

The prevalence of diabetes has increased rapidly throughout the world in recent years. Currently, approximately 463 million people are living with diabetes, and the number has tripled over the last two decades. Here, we describe the global epidemiology of diabetes in 2019 and forecast the trends to 2030 and 2045 in China, India, USA, and the globally. The gut microbiota plays a major role in metabolic diseases, especially diabetes. In this review, we describe the interaction between diabetes and gut microbiota in three aspects: probiotics, antidiabetic medication, and diet. Recent findings indicate that probiotics, antidiabetic medications, or dietary interventions treat diabetes by shifting the gut microbiome, particularly by raising beneficial bacteria and reducing harmful bacteria. We conclude that targeting the gut microbiota is becoming a novel therapeutic strategy for diabetes.

The etiology of many neurological diseases affecting the central nervous system (CNS) is unknown and still needs more effective and specific therapeutic approaches. Gene therapy has a promising future in treating neurodegenerative disorders by correcting the genetic defects or by therapeutic protein delivery and is now an attraction for neurologists to treat brain disorders, like Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, spinocerebellar ataxia, epilepsy, Huntington's disease, stroke, and spinal cord injury. Gene therapy allows the transgene induction, with a unique expression in cells' substrate. This article mainly focuses on the delivering modes of genetic materials in the CNS, which includes viral and non-viral vectors and their application in gene therapy. Despite the many clinical trials conducted so far, data have shown disappointing outcomes. The efforts done to improve outcomes, efficacy, and safety in the identification of targets in various neurological disorders are also discussed here. Adapting gene therapy as a new therapeutic approach for treating neurological disorders seems to be promising, with early detection and delivery of therapy before the neuron is lost, helping a lot the development of new therapeutic options to translate to the clinic.

Covid-19 disease created a havoc since 2019, affected large number of number of people over worldwide. As the second wave is receding, we will be receiving patients with the long-term effects of Covid-19 for the surgeries either for their primary disease or for the complications arising from the Covid-19. Primarily, the Covid-19 is a disease affecting the pulmonary and cardiac system, many other systems including renal, hematology, central nervous, endocrine etc. also damaged with the same. Various endocrine glands are being involved in Covid-19 disease like pancreas, thyroid, pituitary, adrenals, reproductive system etc. as they are highly expressed with ACE. This may even lead to the permanent damage. Because of the unfamiliarity with the disease, plausible impact on the endocrine functions is still unclear. This article elaborates various endocrine manifestations of SARS Cov and SARS Cov-2 for better understanding and management of Covid-19 recovered patients. Keywords: SARS Cov, SARS Cov­2, Covid­19, Endocrinopathies.