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The swift rise of antibiotic resistance, coupled with limited new antibiotic discovery, presents a significant hurdle to global public health, demanding innovative therapeutic solutions. Recently, collateral sensitivity (CS), the phenomenon in which resistance to one antibiotic increases vulnerability to another, has come to light as a potential path forward in this attempt. Targeting either unidirectional or reciprocal CS holds promise for constraining the emergence of drug resistance and notably enhancing treatment outcomes. Typically, the alteration of bacterial physiology, such as bacterial membrane potential, expression of efflux pumps, cell wall structures, and endogenous enzymatic actions, are involved in evolved collateral sensitivity. In this review, we present a thorough overview of CS in antibiotic therapy, including its definition, importance, and underlying mechanisms. We describe how CS can be exploited to prevent the emergence of resistance and enhance the results of treatment, but we also discuss the challenges and restrictions that come with implementing this practice. Our review underscores the importance of continued exploration of CS mechanisms in the broad spectrum and clinical validation of therapeutic approaches, offering insights into its role as a valuable tool in combating antibiotic resistance. [ABSTRACT FROM AUTHOR]

Abstract In the realm of cancer research, the tumor microenvironment (TME) plays a crucial role in tumor initiation and progression, shaped by complex interactions between cancer cells and surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted by various cellular constituents within the TME, including immune cells, cancer-associated fibroblasts, and cancer cells themselves. These cytokines facilitate intricate communication networks that significantly influence tumor initiation, progression, metastasis, and immune suppression. Pyroptosis contributes to TME remodeling by promoting the release of pro-inflammatory cytokines and sustaining chronic inflammation, impacting processes such as immune escape and angiogenesis. However, challenges remain due to the complex interplay among cytokines, pyroptosis, and the TME, along with the dual effects of pyroptosis on cancer progression and therapy-related complications like cytokine release syndrome. Unraveling these complexities could facilitate strategies that balance inflammatory responses while minimizing tissue damage during therapy. This review delves into the complex crosstalk between cytokines, pyroptosis, and the TME, elucidating their contribution to tumor progression and metastasis. By synthesizing emerging therapeutic targets and innovative technologies concerning TME, this review aims to provide novel insights that could enhance treatment outcomes for cancer patients.

Extracellular vesicles (EVs) are nanovesicles containing bioactive molecules including proteins, nucleic acids and lipids that mediate intercellular and interorgan communications, holding promise as potential therapeutics for multiple diseases. Adipose tissue (AT) serves as a dynamically distributed energy storage organ throughout the body, whose accumulation leads to obesity, a condition characterized by infiltration with abundant immune cells. Emerging evidence has illustrated that EVs secreted by AT are the novel class of adipokines that regulate the homeostasis between AT and peripheral organs. However, most of the studies focused on the investigations of EVs derived from adipocytes or adipose-derived stem cells (ADSCs), the summarization of functions in cellular and inter-organ crosstalk of EVs directly derived from adipose tissue (AT-EVs) are still limited. Here, we provide a systemic summary on the key components and functions of EVs derived from healthy adipose tissue, showing their significance on the tissue recovery and metabolic homeostasis regulation. Also, we discuss the harmful influences of EVs derived from obese adipose tissue on the distal organs. Furthermore, we elucidate the potential applications and constraints of EVs from healthy patients lipoaspirates as therapeutic agents, highlighting the potential of AT-EVs as a valuable biological material with broad prospects for future clinical use. [ABSTRACT FROM AUTHOR]

Background: Hyposmia in Parkinson's disease (PD) had been studied before but had not been detailed by its temporal progression. This study observed how each olfactory subtype evolved in terms of motor symptoms, cardiac sympathetic innervation, and cognition. Methods: Two hundred and three early PD patients were classified as normosmia, hyposmia-converter (hypo-converter), and hyposmia. Their presynaptic monoamine availability at the time of diagnosis was assessed by positron emission tomography imaging using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and compared across the subtypes. Motor symptoms were evaluated in all patients, cardiac denervation was examined in 183 patients, and cognition in 195 patients were assessed using a neuropsychological battery. The domains were re-assessed 2–4 times, and the longitudinal data were analyzed to discern the natural course of each subtype. Results: Twenty-nine (14.3%) patients belonged to the normosmia group, 34 (16.7%) to the hypo-converter group, and the rest to the hyposmia (69.0%) group. 85.7% of the total population became hyposmic during an average 3 years of follow-up. The baseline motor symptoms, cardiac denervation, and cognition were comparable across the olfactory subtypes. Across the subtypes, a decline in the presynaptic monoamine densities of the caudate, especially the ventral-anterior subdivisions, correlated inversely with olfaction dysfunction. Over time, motor and cardiac denervation burdens worsened regardless of olfactory subtypes, but hypo-converters experienced faster cognitive deterioration than the other two groups. Conclusions: The results suggest that the olfactory subtypes have differential significance along the disease course, which might reflect the involvement of different neuro-biochemical circuitries. [ABSTRACT FROM AUTHOR]

Hashimoto's thyroiditis (HT) is not only the most frequent autoimmune thyroid disease (AITD), but it also has a significant impact on patients' health-related quality of life (HRQoL), and it has been variably associated with differentiated thyroid carcinoma. Even though its pathogenesis is still incompletely understood, oxidative stress is believed to play an important role. Hypothyroidism related to later stages of HT can be treated with levothyroxine substitution therapy; various approaches such as selenium supplementation and iodine-restricted diets have been proposed as disease-modifying treatments for earlier stages, and even thyroidectomy has been suggested for refractory cases of painful HT. Nevertheless, many patients still report suboptimal HRQoL, highlighting an unmet medical need in this area. The concepts and approaches of traditional Chinese medicine (TCM) in treating HT are not broadly known in the West. Here, we provide an overview of TCM for HT, including combinations of TCM with selenium. We encompass evidence from clinical trials and other studies related to complex TCM prescriptions, single herbs used in TCM, and phytochemicals; wherever possible, we delineate the probable underlying molecular mechanisms. The findings show that the main active components of TCM for HT have commonly known or presumed antioxidant and anti-inflammatory activities, which may account for their potential utility in HT. Further exploring the practices of TCM for HT and combining them with evidence- and mechanism-based approaches according to Western standards may help to identify new strategies to alter the clinical course of the disease and/or to treat patients' symptoms better and improve their HRQoL. [ABSTRACT FROM AUTHOR]

Background Circular RNAs (circRNAs) are identified as a novel family of endogenous RNA molecules through ‘back-splicing’ and covalently linked at the 5′ and 3′ ends. Emerging researches have demonstrated circRNAs are stable and abundant in exosomes called exosomal circRNAs (exo-circRNA).Materials and methods We searched recent studies and references to summary the research progress of exosomal circRNA.Results Recent studies have revealed that exosome-derived circRNAs including exo-CDR1as, exo-circRanGAP1, exo-circIAR play vital roles in cell proliferation and apoptosis, epithelial mesenchymal transition, invasion and metastasis, angiogenesis, immune evasion, cellular crosstalk, cancer cachexia through a variety of biological mechanisms, such as serving as microRNA sponges, interacting with RNA binding proteins, regulating gene transcription, N6-Methyladenosine modification and so on. Due to their characteristics of origin, structure, properties and biological functions, exo-circRNAs are expected to apply in precious diagnosis and prognostic indicators, improving drug and radiation resistance and sensitivity, becoming biological therapeutic targets.Conclusion We summarize the update of digestive malignancies associated exo-circRNAs in biogenesis, biological functions, molecular mechanisms, clinical implications, potential applications and experimental technique in order to effectively promote transformation and application in the future.

The swift rise of antibiotic resistance, coupled with limited new antibiotic discovery, presents a significant hurdle to global public health, demanding innovative therapeutic solutions. Recently, collateral sensitivity (CS), the phenomenon in which resistance to one antibiotic increases vulnerability to another, has come to light as a potential path forward in this attempt. Targeting either unidirectional or reciprocal CS holds promise for constraining the emergence of drug resistance and notably enhancing treatment outcomes. Typically, the alteration of bacterial physiology, such as bacterial membrane potential, expression of efflux pumps, cell wall structures, and endogenous enzymatic actions, are involved in evolved collateral sensitivity. In this review, we present a thorough overview of CS in antibiotic therapy, including its definition, importance, and underlying mechanisms. We describe how CS can be exploited to prevent the emergence of resistance and enhance the results of treatment, but we also discuss the challenges and restrictions that come with implementing this practice. Our review underscores the importance of continued exploration of CS mechanisms in the broad spectrum and clinical validation of therapeutic approaches, offering insights into its role as a valuable tool in combating antibiotic resistance.

Introduction: Since the first experimentally proven tyrosine kinase inhibitor (TKI) imatinib was introduced in the clinical setting, TKIs have attracted widespread attention because of their remarkable therapeutic effects and improvement of survival rates. TKIs are small-molecule, multi-target, anti-cancer agents that target different tyrosine kinases and block downstream signaling. Adverse Reactions and Concerns: However, with in-depth research on TKI drugs, the adverse reactions—for example, thyroid dysfunction—have become a concern and thus have attracted the attention of numerous researchers. Thyroid dysfunction, especially hypothyroidism, that occurs in high incidence during TKI therapy has a close relationship with treatment efficacy, but the mechanism of TKI-induced thyroid dysfunction is obscure. Discussion: This review discusses the epidemiology, possible mechanisms, and clinical significance of hypothyroidism in cancer patients treated with TKI. [ABSTRACT FROM AUTHOR]

Background: Acute ischemic stroke remains a major contributor to mortality and disability worldwide. The use of hypothermia has emerged as a promising neuroprotective strategy, with proven effectiveness in cardiac arrest and neonatal hypoxic-ischemic injury. Summary: This review explores the therapeutic potential of hypothermia in ischemic stroke by examining its impact on poststroke inflammatory responses. We synthesized evidence from basic and clinical studies to illustrate the inhibitory effects of hypothermia on poststroke brain inflammation. The underlying mechanisms include modulation of microglial activation and polarization; downregulation of key inflammatory pathways such as MAPKs, NF-KB, and JAK/STAT; protection of the blood-brain barrier integrity; and reduction of immune cell infiltration into the brain. We also discuss the current limitations of hypothermia treatment in clinical practice and highlight future research directions for optimizing protocols and evaluating its clinical efficacy in stroke patients. Key Messages: Therapeutic hypothermia (TH) has evolved significantly with advancements in medical technologies, especially with the introduction of automated cooling devices, both intravascular and surface based. However, a refined, highly individualized, and effective hypothermia protocol may stand robust against the devastating consequences of ischemic stroke, and we think it should become the future development goal. [ABSTRACT FROM AUTHOR]

Simple Summary: In the last two decades, the use of small molecules as chemical inhibitors of different targets in signaling pathways has been of great interest for therapeutic purposes. In the case of multiple myeloma, it has not been an exception, with researchers focusing in part on the p38 pathway. However, the search continues for more specific p38 inhibitors according to differently expressed p38 isoforms. One of the latest reviews on this topic is from 10 years ago, so in this review, we highlight the research in this context from the last 10 years, showing the advances in the use of more effective inhibitors alone or in combination with other therapeutic agents. Resistance to therapy and disease progression are the main causes of mortality in most cancers. In particular, the development of resistance is an important limitation affecting the efficacy of therapeutic alternatives for cancer, including chemotherapy, radiotherapy, and immunotherapy. Signaling pathways are largely responsible for the mechanisms of resistance to cancer treatment and progression, and multiple myeloma is no exception. p38 mitogen-activated protein kinase (p38) is downstream of several signaling pathways specific to treatment resistance and progression. Therefore, in recent years, developing therapeutic alternatives directed at p38 has been of great interest, in order to reverse chemotherapy resistance and prevent progression. In this review, we discuss recent findings on the role of p38, including recent advances in our understanding of its expression and activity as well as its isoforms, and its possible clinical role based on the mechanisms of resistance and progression in multiple myeloma. [ABSTRACT FROM AUTHOR]

Hashimoto’s thyroiditis (HT) is not only the most frequent autoimmune thyroid disease (AITD), but it also has a significant impact on patients’ health-related quality of life (HRQoL), and it has been variably associated with differentiated thyroid carcinoma. Even though its pathogenesis is still incompletely understood, oxidative stress is believed to play an important role. Hypothyroidism related to later stages of HT can be treated with levothyroxine substitution therapy; various approaches such as selenium supplementation and iodine-restricted diets have been proposed as disease-modifying treatments for earlier stages, and even thyroidectomy has been suggested for refractory cases of painful HT. Nevertheless, many patients still report suboptimal HRQoL, highlighting an unmet medical need in this area. The concepts and approaches of traditional Chinese medicine (TCM) in treating HT are not broadly known in the West. Here, we provide an overview of TCM for HT, including combinations of TCM with selenium. We encompass evidence from clinical trials and other studies related to complex TCM prescriptions, single herbs used in TCM, and phytochemicals; wherever possible, we delineate the probable underlying molecular mechanisms. The findings show that the main active components of TCM for HT have commonly known or presumed antioxidant and anti-inflammatory activities, which may account for their potential utility in HT. Further exploring the practices of TCM for HT and combining them with evidence- and mechanism-based approaches according to Western standards may help to identify new strategies to alter the clinical course of the disease and/or to treat patients’ symptoms better and improve their HRQoL.

This study investigated clinical aspects of the traditional ear impression and 3D ear scanning techniques. Adult earmold-users and non-users participated in this study. The earmold-users also participated in the earmold comfort comparison study by wearing earmolds from both techniques, one set a week according to a randomized sequence. Multiple clinical aspects of both techniques according to the participants and audiology professionals were recorded. Results revealed a preference for the 3D-scanning technique, which was perceived as more comfortable although both techniques were perceived as safe. Although the earmolds might have issues from both techniques, there was no significant difference in the perception of earmolds. Experience with the specific technique can affect the responses from the professionals. Compared to the traditional technique, 3D-scans had higher fixed but less variable costs and procedure times. A special clinical case was included and indicated that 3D-scans could be an option for specific patients. This study led to a better understanding of the two techniques clinically. With increasing involvement of new technology and more young professionals joining the profession of audiology, 3D ear scanning could be a viable consideration for audiology practices. [ABSTRACT FROM AUTHOR]

Epilepsy is the most common neurological disorder with a worldwide incidence of 20% and a treatment failure rate of 25–30%. The fluctuation in serum levels, efficacy and safety of antiepileptic drugs can be attributed to single nucleotide polymorphisms of genes encoding their respective proteins involved in drug metabolism. The present study attempted to evaluate the pharmacogenetic variants of CYP2C9 and CYP2C19 associated with adverse reactions induced by antiepileptic drugs used in Peru. Few studies were found to significantly associate the CYP2C9*2, CYP2C9*3, CYP2C19*2, and CYP2C19*3 single nucleotide polymorphisms with elevated serum levels of valproic acid and carbamazepine, and valproic acid induction of hyperammonemia, and adverse reactions cutaneous for carbamazepine. There is further evidence of a significant association of CYP2C9*2/CYP2C9*3 with severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and epidermal necrolysis (TEN) phenytoin-induced. CYP2C9*3 may be a pharmacogenetic biomarker for such a drug. It is proposed to reduce the dose of drugs for intermediate and poor metabolizers. No pharmacogenetic studies were found in patients with epilepsy in Peruvian populations. It is concluded that this review could help physicians in the prediction and prevention of adverse reactions induced by antiepileptic drugs, as well as to improve their pharmacotherapeutic results. It could also be used as scientific evidence to carry out pharmacogenetic and precision medicine studies in Peruvian patients with epilepsy, due to their tricontinental and Latin American ancestry. [ABSTRACT FROM AUTHOR]

This study investigated clinical aspects of the traditional ear impression and 3D ear scanning techniques. Adult earmold-users and non-users participated in this study. The earmold-users also participated in the earmold comfort comparison study by wearing earmolds from both techniques, one set a week according to a randomized sequence. Multiple clinical aspects of both techniques according to the participants and audiology professionals were recorded. Results revealed a preference for the 3D-scanning technique, which was perceived as more comfortable although both techniques were perceived as safe. Although the earmolds might have issues from both techniques, there was no significant difference in the perception of earmolds. Experience with the specific technique can affect the responses from the professionals. Compared to the traditional technique, 3D-scans had higher fixed but less variable costs and procedure times. A special clinical case was included and indicated that 3D-scans could be an option for specific patients. This study led to a better understanding of the two techniques clinically. With increasing involvement of new technology and more young professionals joining the profession of audiology, 3D ear scanning could be a viable consideration for audiology practices.

More than 1.8 million of new cases of lung cancer (LC) are registered each year worldwide. LC is the leading cause of cancer death in both developing and developed countries, and the 5 years survival rate is as low as 19 %. Many factors explain such unsatisfactory outcomes, including the LC diagnosis at an advanced stage, when the currently available treatments can rarely provide cure. Biomarkers are used to assess the development risks, screening, diagnosis, monitoring, and prognosis, and to personalize the LC treatment. Clinical use of biomarkers is essential for the identification of a high-risk group for screening for LC and differentiating early LC from benign pulmonary lesions. Current trends in the development of LC biomarkers involve the integration of molecular biomarkers with clinical and radiological characteristics using artificial intelligence for the development of imaging biomarkers, and using highly sensitive technologies such as next-generation sequencing for molecular research. LC biomarkers are now at all stages of development, from discovery to clinical trials requiring high-quality clinical validation. Reliable biomarkers are especially needed to differentiate malignant and benign lesions in the lung tissue and to identify those at greatest risk of developing lung cancer. Scientific advances in understanding LC have led to the development of biomarkers that demonstrate sufficient accuracy in clinical validation studies. Promising trends in the development of LC biomarkers include highly sensitive and increasingly accessible NGS and radiomics technologies, along with the use of easily collected biomaterials, which in combination with other tumor characteristics contribute to the development of biomarkers for assessing the LC development risks, diagnosis, monitoring, prognosis and personalized therapy. This review focuses on the development, current application, and future trends in the use of LC biomarkers.

Introduction: Median Nerve (MN) originated from medial and lateral cords of Brachial Plexus and can be affected by anatomical variations, which may lead to several diagnostic and therapeutic mistakes. This paper aimed to study MN variations investigated by cadaveric studies. Methods: This study is based on research in electronic databases. The full text of all relevant papers has been studied to extend our data. Results: variation of MN distribution in the palm, variation of MN innervation patterns, communication between MN and (Ulnar Nerve) UN and their branches in the forearm, communication between MN and UN and their components in the palm, variation in the course of MN are main MN variation categories containing several subgroups. However, communication between the third common digital nerve of MN and the fourth common digital nerve of UN is the most common MN variation at the distal of upper limbs. Conclusion: decompression of MN entrapped in the carpal tunnel can be considered the essential clinical challenge resulting from MN variations, especially variations including the third common digital nerve.

Exosomes are small extracellular vesicles with a lipid bilayer structure secreted from different cell types which can be found in various body fluids including blood, pleural fluid, saliva and urine. They carry different biomolecules including proteins, metabolites, and amino acids such as microRNAs which are small non-coding RNAs that regulate gene expression and promote cell-to-cell communication. One main function of the exosomal miRNAs (exomiRs) is their role in cancer pathogenesis. Alternation in exomiRs expression could indicate disease progression and can regulate cancer growth and facilitate drug response/resistance. It can also influence the tumour microenvironment by controlling important signaling that regulating immune checkpoint molecules leading to activation of T cell anti-tumour immunity. Therefore, they can be used as potential novel cancer biomarkers and innovative immunotherapeutic agents. This review highlights the use of exomiRs as potential reliable biomarkers for cancer diagnosis, treatment response and metastasis. Finally, discuses their potential as immunotherapeutic agents to regulate immune checkpoint molecules and promote T cell anti-tumour immunity.

The goal of this review was to critically evaluate the research on the effects of Spirulina (SP) supplementation on pathological conditions in the general population, considering its antioxidant, immunomodulatory, and anti-inflammatory properties. On a total of 1621 records screened, eighteen studies published between 2001 and 2020 met the inclusion criteria. Despite variability in research methodology and patient conditions, the findings of these studies generally support the benefits of supplementing diet with SP in subjects with both transmittable and non-transmittable diseases. Improvements were found for all the conditions studied, with the only exception of male infertility. However, the number of clinically controlled trials examining the effects of SP on specific health conditions is still very low, and some studies show medium quality. Further research in this field is needed to confirm the possible clinical role of Spirulina supplementation in parallel with medical therapies. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common liver malignancy that can be developed from hepatitis B and cirrhosis. Many pathophysiological alterations, including hepatitis B virus (HBV) DNA integration, oxidative stress, cytokine release, telomerase homeostasis, mitochondrial damage, epigenetic modification, and tumor microenvironment, are involved in the biological process from hepatitis B to cirrhosis and HCC. N6‐methyladenosine (m6A), as an epitranscriptomic modification of RNAs, can regulate the stability, splicing, degradation, transcription, and translation of downstream target RNAs in HBV and liver cancer cells. m6A regulators (writers, erasers, and readers) play an important role in the pathogenesis of HBV‐associated HCC by regulating cell proliferation, apoptosis, migration, autophagy, differentiation, inflammation, angiogenesis, and tumor microenvironment. This review summarizes the current progress of m6A methylation in the molecular mechanisms, biological functions, and potential clinical implications of HBV‐associated HCC. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) are identified as a novel family of endogenous RNA molecules through 'back-splicing' and covalently linked at the 5' and 3' ends. Emerging researches have demonstrated circRNAs are stable and abundant in exosomes called exosomal circRNAs (exo-circRNA)., Materials and Methods: We searched recent studies and references to summary the research progress of exosomal circRNA., Results: Recent studies have revealed that exosome-derived circRNAs including exo-CDR1as, exo-circRanGAP1, exo-circIAR play vital roles in cell proliferation and apoptosis, epithelial mesenchymal transition, invasion and metastasis, angiogenesis, immune evasion, cellular crosstalk, cancer cachexia through a variety of biological mechanisms, such as serving as microRNA sponges, interacting with RNA binding proteins, regulating gene transcription, N6-Methyladenosine modification and so on. Due to their characteristics of origin, structure, properties and biological functions, exo-circRNAs are expected to apply in precious diagnosis and prognostic indicators, improving drug and radiation resistance and sensitivity, becoming biological therapeutic targets., Conclusion: We summarize the update of digestive malignancies associated exo-circRNAs in biogenesis, biological functions, molecular mechanisms, clinical implications, potential applications and experimental technique in order to effectively promote transformation and application in the future.

In the realm of cancer research, the tumor microenvironment (TME) plays a crucial role in tumor initiation and progression, shaped by complex interactions between cancer cells and surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted by various cellular constituents within the TME, including immune cells, cancer-associated fibroblasts, and cancer cells themselves. These cytokines facilitate intricate communication networks that significantly influence tumor initiation, progression, metastasis, and immune suppression. Pyroptosis contributes to TME remodeling by promoting the release of pro-inflammatory cytokines and sustaining chronic inflammation, impacting processes such as immune escape and angiogenesis. However, challenges remain due to the complex interplay among cytokines, pyroptosis, and the TME, along with the dual effects of pyroptosis on cancer progression and therapy-related complications like cytokine release syndrome. Unraveling these complexities could facilitate strategies that balance inflammatory responses while minimizing tissue damage during therapy. This review delves into the complex crosstalk between cytokines, pyroptosis, and the TME, elucidating their contribution to tumor progression and metastasis. By synthesizing emerging therapeutic targets and innovative technologies concerning TME, this review aims to provide novel insights that could enhance treatment outcomes for cancer patients., Competing Interests: Declarations. Ethical approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Lumbrical muscles originate in the palm from the 4 tendons of the flexor digitorum profundus and course distally along the radial side of the corresponding metacarpophalangeal joints, in front of the deep transverse metacarpal ligament. The first and second lumbrical muscles are typically innervated by the median nerve, and third and fourth by the ulnar nerve. A plethora of lumbrical muscle variants has been described, ranging from muscles' absence to reduction in their number or presence of accessory slips. The current cadaveric study highlights typical and variable neural supply of lumbrical muscles. Materials: Eight (3 right and 5 left) fresh frozen cadaveric hands of 3 males and 5 females of unknown age were dissected. From the palmar wrist crease, the median and ulnar nerve followed distally to their terminal branches. The ulnar nerve deep branch was dissected and lumbrical muscle innervation patterns were noted. Results: The frequency of typical innervations of lumbrical muscles is confirmed. The second lumbrical nerve had a double composition from both the median and ulnar nerves, in 12.5% of the hands. The thickest branch (1.38 mm) originated from the ulnar nerve and supplied the third lumbrical muscle, and the thinnest one (0.67 mm) from the ulnar nerve and supplied the fourth lumbrical muscle. In 54.5%, lumbrical nerve bifurcation was identified. Conclusion: The complex innervation pattern and the peculiar anatomy of branching to different thirds of the muscle bellies are pointed out. These findings are important in dealing with complex and deep injuries in the palmar region, including transmetacarpal amputations. [ABSTRACT FROM AUTHOR]

miRNAs are non-coding RNA sequences of approximately 22 nucleotides that interact with genes by inhibiting their translation through binding to their 3′ or 5′ UTR regions. Following their discovery, the role they play in the development of various pathologies, particularly cancer, has been studied. In this context, miR-7 is described as an important factor in the development of cancer because of its role as a tumor suppressor, regulating a large number of genes involved in the development and progression of cancer. Recent data support the function of miR-7 as a prognostic biomarker in cancer, and miR-7 has been proposed as a strategy in cancer therapy. In this work, the role of miR-7 in various types of cancer is reviewed, illustrating its regulation, direct targets, and effects, as well as its possible relationship to the clinical outcome of cancer patients. [ABSTRACT FROM AUTHOR]

BackgroundBreast cancer is the most common malignant tumor among women worldwide, and breast cancer stem cells (BCSCs) are believed to be the source of tumorigenesis. New findings suggest that small nucleolar RNAs (snoRNAs) play a significant role in tumor development.MethodsThe Cancer Genome Atlas (TCGA) and Kaplan–Meier survival analysis were used to demonstrate expression and survival of SNORA38 signature. In situ hybridization (ISH) and immunohistochemical (IHC) were conducted to analyze the correlation between SNORA38 and stemness biomarker in 77 BC samples. Gene Set Enrichment Analysis (GSEA) was performed to investigate the mechanisms related to SNORA38 expression in BC. Real-time qPCR was employed to evaluate the expression of SNORA38 in breast cancer cell lines.ResultsIn the public database and patients’ biopsies, SNORA38 was significantly up-regulated in breast cancer. Furthermore, the expression of SNORA38 was significantly correlated with tumor size, lymph node metastasis, and TNM stage, among which tumor size was an independent factor for SNORA38 expression. Higher SNORA38 expression was associated with shorter overall survival (OS). Meanwhile, SNORA38 was positively associated with the stem cell marker OCT-4, which suggested that SNORA38 might be related to breast cancer stemness.ConclusionsSNORA38 is an important carcinogenic snoRNA in breast cancer and might be a prognostic biomarker for breast cancer.

The diagnosis of hepatocellular carcinoma (HCC) is made at a relatively advanced stage resulting in poor prognosis. Alpha-fetoprotein and liver ultrasound have limited accuracy as biomarkers in HCC. Liver biopsy provides information on tumor biology; however, it is invasive and holds high threat of tumor seeding. Thus, more accurate and less invasive approaches are needed Highly sensitive liquid biopsy assays have made possible the detection and analysis of cells or organelles such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and tumor-derived exosomes. Here, we focus on CTCs and ctDNA components of liquid biopsy and their clinical application as diagnostic, prognostic, and predictive biomarkers in HCC. Unlike tissue biopsy, liquid biopsy involves attaining a sample at several time frames in an easy and a non-invasive manner. They have been efficacious in detecting and classifying cancer, in predicting treatment response, in monitoring disease relapse and in identifying mechanisms of resistance to targeted therapies. Although interesting and highly promising, liquid biopsy techniques still have many obstacles to overcome before their wide spread clinical application sees the light. It is expected that these techniques will be incorporated into traditional methodologies for better diagnostic, predictive and prognostic results. [ABSTRACT FROM AUTHOR]

microRNAs (miRNAs) are a type of small endogenous non-coding RNAs composed of 20-22 nucleotides, which can regulate the expression of a gene by targeting 3' untranslated region (3'-UTR) of mRNA. Many studies have reported that miRNAs are involved in the occurrence and progression of human diseases, including malignant tumors. miR-1224 plays significant roles in different tumors, including tumor proliferation, metastasis, invasion, angiogenesis, biological metabolism, and drug resistance. Mostly, it serves as a tumor suppressor. With accumulating proofs of miR-1224, it can act as a potential bio-indicator in the diagnosis and prognosis of patients with cancer. In this article, we review the characteristics and research progress of miR-1224 and emphasize the regulation and function of miR-1224 in different cancer. Furthermore, we conclude the clinical implications of miR-1224. This review may provide new horizons for deeply understanding the role of miR-1224 as biomarkers and therapeutic targets in human cancer. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most disseminated diseases across the globe engaging the digestive system. Various therapeutic methods from traditional to the state-of-the-art ones have been applied in CRC patients, however, the attempts have been unfortunate to lead to a definite cure. MiRNAs are a smart group of non-coding RNAs having the capabilities of regulating and controlling coding genes. By utilizing this stock-in-trade biomolecules, not only disease’s symptoms can be eliminated, there may also be a good chance for the complete cure of the disease in the near future. Herein, we provide a comprehensive review delineating the therapeutic relationship between miRNAs and CRC. To this, various clinical aspects of miRNAs which act as a tumor suppressor and/or an oncogene, their underlying cellular processes and clinical outcomes, and, in particular, their effects and expression level changes in patients treated with chemo- and radiotherapy are discussed. Finally, based on the results deducted from scientific research studies, therapeutic opportunities based on targeting/utilizing miRNAs in the preclinical as well as clinical settings are highlighted.

Background: Recent studies have shown that alpha-1,3-mannosyltransferase (ALG3) promoted tumorigenesis and progression in multiple cancer types. Our study planned to explore the clinical implication and potential function of ALG3 in hepatocellular carcinoma.Materials and Methods: Data from public databases were used to analyze the ALG3 expression and its impact on the clinical significance of patients with HCC. The ALG3 expression was confirmed by qRT-PCR and Western blot. Immunohistochemistry was used to confirm the ALG3 expression and explore its clinical implication in HCC. KEGG, GO, and GSEA enrichment analyses were utilized to explore the biological pathways related to ALG3 in HCC. TIMER2.0 was applied to assess the association between ALG3 and immune infiltration. CCK8, MTT, and transwell assays were used to investigate the role of ALG3 downregulation in HCC cell lines.Results: qRT-PCR, WB, and IHC proved ALG3 was highly overexpressed in HCC tissues. The Kaplan–Meier analysis verified the overexpression of ALG3 was related to poor overall survival (p < 0.001). Multivariate cox regression analysis showed that the high ALG3 expression was an independent risk prognostic factor. GSEA and TIMER2.0 predicted that ALG3 participates in cell differentiation and cycle and correlates with immune cell infiltration. Transwell assay results showed that ALG3 silencing also impaired the invasion ability of HCC cells.Conclusion: ALG3 was overexpressed and considered a potential indicator of survival in HCC, and our findings provided a novel therapeutic target for HCC.

microRNAs (miRNAs) are a type of small endogenous non-coding RNAs composed of 20-22 nucleotides, which can regulate the expression of a gene by targeting 3’ untranslated region (3’-UTR) of mRNA. Many studies have reported that miRNAs are involved in the occurrence and progression of human diseases, including malignant tumors. miR-1224 plays significant roles in different tumors, including tumor proliferation, metastasis, invasion, angiogenesis, biological metabolism, and drug resistance. Mostly, it serves as a tumor suppressor. With accumulating proofs of miR-1224, it can act as a potential bio-indicator in the diagnosis and prognosis of patients with cancer. In this article, we review the characteristics and research progress of miR-1224 and emphasize the regulation and function of miR-1224 in different cancer. Furthermore, we conclude the clinical implications of miR-1224. This review may provide new horizons for deeply understanding the role of miR-1224 as biomarkers and therapeutic targets in human cancer.

Introduction: Median Nerve (MN) originated from medial and lateral cords of Brachial Plexus and can be affected by anatomical variations, which may lead to several diagnostic and therapeutic mistakes. This paper aimed to study MN variations investigated by cadaveric studies. Methods: This study is based on research in electronic databases. The full text of all relevant papers has been studied to extend our data. Results: variation of MN distribution in the palm, variation of MN innervation patterns, communication between MN and (Ulnar Nerve) UN and their branches in the forearm, communication between MN and UN and their components in the palm, variation in the course of MN are main MN variation categories containing several subgroups. However, communication between the third common digital nerve of MN and the fourth common digital nerve of UN is the most common MN variation at the distal of upper limbs. Conclusion: decompression of MN entrapped in the carpal tunnel can be considered the essential clinical challenge resulting from MN variations, especially variations including the third common digital nerve. [ABSTRACT FROM AUTHOR]

Background Radiopacity is a critical property for root canal sealers as it allows for the assessment of the material's placement and quality within the root canal system on radiographic images. The study aimed to evaluate the radiopacity of calcium silicate-based and resin-based materials using direct digital radiography, employing an aluminium step wedge according to American National Standards Institute/International Organization for Standardization (ANSI/ISO) standard protocols for testing the radiopacity of root canal sealers. This study seeks to determine the effectiveness of these materials in meeting the required standards for clinical use. Methodology The materials tested were AH Plus, Apexit Plus, Biodentine and MTA Fillapex in circular disc form and radiographed alongside the aluminium step wedge using direct digital radiography to determine the radiopacity using grey-pixel values. All the materials, viz., AH Plus, Apexit Plus, Biodentine and MTA Fillapex were found satisfactorily radiopaque and met the minimum radiopacity standard, that is, minimum 3mm of aluminium recommended by ANSI/American Dental Association (ADA) Specification No. 57. Results AH Plus exhibited the highest radiopacity with values of 222.54 mm Al Eq (isodensity) and 220.88 mm Al Eq (densitometric), significantly surpassing Apexit Plus, Fillapex and Biodentine (p < 0.001). Apexit Plus and Fillapex showed no significant difference between them (p = 0.238), but both were significantly higher than Biodentine (p < 0.001). Biodentine had the lowest radiopacity among all the sealers tested. Conclusion All the tested materials met the ANSI/ADA minimum radiopacity standard, demonstrating their suitability for clinical use. The materials varied in their levels of radiopacity, demonstrating that they are adequately visible on radiographic images for effective assessment in root canal treatments., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Azhar et al.)

Extracellular vesicles (EVs) are nanovesicles containing bioactive molecules including proteins, nucleic acids and lipids that mediate intercellular and inter-organ communications, holding promise as potential therapeutics for multiple diseases. Adipose tissue (AT) serves as a dynamically distributed energy storage organ throughout the body, whose accumulation leads to obesity, a condition characterized by infiltration with abundant immune cells. Emerging evidence has illustrated that EVs secreted by AT are the novel class of adipokines that regulate the homeostasis between AT and peripheral organs. However, most of the studies focused on the investigations of EVs derived from adipocytes or adipose-derived stem cells (ADSCs), the summarization of functions in cellular and inter-organ crosstalk of EVs directly derived from adipose tissue (AT-EVs) are still limited. Here, we provide a systemic summary on the key components and functions of EVs derived from healthy adipose tissue, showing their significance on the tissue recovery and metabolic homeostasis regulation. Also, we discuss the harmful influences of EVs derived from obese adipose tissue on the distal organs. Furthermore, we elucidate the potential applications and constraints of EVs from healthy patients lipoaspirates as therapeutic agents, highlighting the potential of AT-EVs as a valuable biological material with broad prospects for future clinical use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han, Ye and Liu.)

Objective: Inborn errors of immunity (IEI) are a heterogeneous group of disorders, affecting different components of the immune system. Over 450 IEI related genes have been identified, with new genes continually being recognized. This makes the early application of next-generation sequencing (NGS) as a diagnostic method in the evaluation of IEI a promising development. We aimed to provide an overview of the diagnostic yield and time to diagnosis in a cohort of patients suspected of IEI and evaluated by an NGS based IEI panel early in the diagnostic trajectory in a multicenter setting in the Netherlands. Study Design: We performed a prospective observational cohort study. We collected data of 165 patients with a clinical suspicion of IEI without prior NGS based panel evaluation that were referred for early NGS using a uniform IEI gene panel. The diagnostic yield was assessed in terms of definitive genetic diagnoses, inconclusive diagnoses and patients without abnormalities in the IEI gene panel. We also assessed time to diagnosis and clinical implications. Results: For children, the median time from first consultation to diagnosis was 119 days versus 124 days for adult patients (U=2323; p=0.644). The median turn-around time (TAT) of genetic testing was 56 days in pediatric patients and 60 days in adult patients (U=1892; p=0.191). A definitive molecular diagnosis was made in 25/65 (24.6%) of pediatric patients and 9/100 (9%) of adults. Most diagnosed disorders were identified in the categories of immune dysregulation (n=10/25; 40%), antibody deficiencies (n=5/25; 20%), and phagocyte diseases (n=5/25; 20%). Inconclusive outcomes were found in 76/165 (46.1%) patients. Within the patient group with a genetic diagnosis, a change in disease management occurred in 76% of patients. Conclusion: In this cohort, the highest yields of NGS based evaluation for IEI early in the diagnostic trajectory were found in pediatric patients, and in the disease categories immune dysregulation and phagocyte diseases. In cases where a definitive diagnosis was made, this led to important disease management implications in a large majority of patients. More research is needed to establish a uniform diagnostic pathway for cases with inconclusive diagnoses, including variants of unknown significance. [ABSTRACT FROM AUTHOR]

Parietal emissary foramina (PEF) are an important structure which the parietal emissary vein passes through. Aims of this study were to study morphometry of the PEF and its clinical implications. The present study examined in 800 parietal bones (400 Thai skulls; 200 males and 200 females). A total of 587 emissary foramina were found in 344 skulls. The PEF were found on the right side (298), left side (256). One hundred fifty-five unilateral, 189 bilateral, and 33 center of PEF were found in our study. The average of foramina to sagittal suture were 5.67 ± 2.73 mm on the right and 5.91 ± 2.37 mm on the left in male, while in female it was 5.28 ± 2.61 mm on the right and 5.48 ± 2.54 mm on the left. The shape was mostly circular with mean diameter of 1.27 ± 0.56 mm on the right, 1.23 ± 0.52 on the left and 1.11 ± 0.49 mm at the center in male. In female, the mean diameter of 1.19 ± 0.42 mm on the right, 1.12 ± 0.41 mm on the left and 1.60 ± 0.92 mm at the center. The ratio of distance from the external occipital protuberance (EOP)to PEF and to glabella in males on the right side is 0.342 cm. (3/8) and 0.349 cm. (3/8) on the left side. While the ratio of females is 0.367 cm. (3/8) and 0.388 cm. (3/8), respectively. Our finding obtained in this study scientists can be essentially benefited for anatomists, radiologists, neurosurgeons, and forensic to aware this anatomical structure. [ABSTRACT FROM AUTHOR]

This work investigated the clinical prognostic implications and biological function of plasma soluble programmed cell death ligand 1 in breast cancer patients. Plasma sPD-L1 levels of recurrent/metastatic breast cancer patients were determined, and the association of sPD-L1 levels and metastatic progression-free survival and metastatic overall survival was assessed. The PD-L1 expression on breast cancer cells was analyzed by flow cytometry, and the level of sPD-L1 in the supernatant of breast cancer cells was determined by enzyme-linked immunosorbent assay. Furthermore, the effect of sPD-L1 on the proliferation and apoptosis of T lymphocytes was detected by WST-1 assay and flow cytometry. The plasma sPD-L1 levels in 208 patients with recurrent/metastatic breast cancer before receiving first-line rescue therapy were measured. The optimal cutoff value of plasma sPD-L1 for predicting disease progression was 8.774 ng/ml. Univariate and multivariate analyses identified high sPD-L1 level (≥ 8.774 ng/ml) and visceral metastasis were independent factors associated with poor prognosis. Relevance analysis showed that the plasma sPD-L1 level was weakly associated with some systemic inflammation markers, including white cell count (WBC), absolute monocyte count, and absolute neutrophil count. Furthermore, we found sPD-L1 could be found in supernatant of culture with breast cancer cell line expressing PD-L1 on the cell surface and inhibit T lymphocyte function, playing a negative regulatory role in cellular immunity. sPD-L1 was a good tumor predictive maker in breast cancer and it may play a potentially important role in immune tolerance. [ABSTRACT FROM AUTHOR]

Background: BRCA1 immunohistochemistry (IHC) provides a rapid initial screen to detect BRCA1 dysfunction in ovarian cancer that resulting from genetic alterations. Aim: To assess the expression of BRCA1 protein by IHC analysis among a group of Iraqi ovarian cancer patients to evaluate the patterns of expression and its correlation with the clinicopathological parameters in attempting to evaluate a significance role of BRCA1 gene implication in ovarian cancer. Methods: Forty three paraffin embedded samples of ovarian cancer cases were analyzed for BRCA1dysfunction by IHC analysis. The semi-quantitative approach using modified histochemical score (H-score) was achieved to assess the patterns of BRCA1 gene expression. Results: Complete loss of BRCA1 nuclear expression was detected in 30.2% of the cases while, reduced expression occurred in 46.5% of cases, giving rise to 76.7% of all cases detected with altered BRCA1 nuclear expression. Altered BRCA1 expression was found to be higher in age group ≤ 45 years (78.3%) in comparison with those of ages >45 years. Altered BRCA1 expression was significantly correlated with the high grade and with the unilateral tumor site when compared with the low grade and bilateral tumor site (P≤0.05), and was insignificantly correlated with the high stage ovarian tumors, 11.6% of cases were detected by cytoplasmic BRCA1 expression and no association was found between cytoplasmic expression and tumor grade, stage and tumor site. Conclusion: Altered BRCA1 expression may play a significant role in the progression of ovarian cancer. Recommendation: BRCA1 IHC is a clinically useful approach to detect the BRCA1 dysfunction and the H-score assessment reflects good estimation for BRCA1expression patterns.

ObjectiveInborn errors of immunity (IEI) are a heterogeneous group of disorders, affecting different components of the immune system. Over 450 IEI related genes have been identified, with new genes continually being recognized. This makes the early application of next-generation sequencing (NGS) as a diagnostic method in the evaluation of IEI a promising development. We aimed to provide an overview of the diagnostic yield and time to diagnosis in a cohort of patients suspected of IEI and evaluated by an NGS based IEI panel early in the diagnostic trajectory in a multicenter setting in the Netherlands.Study DesignWe performed a prospective observational cohort study. We collected data of 165 patients with a clinical suspicion of IEI without prior NGS based panel evaluation that were referred for early NGS using a uniform IEI gene panel. The diagnostic yield was assessed in terms of definitive genetic diagnoses, inconclusive diagnoses and patients without abnormalities in the IEI gene panel. We also assessed time to diagnosis and clinical implications.ResultsFor children, the median time from first consultation to diagnosis was 119 days versus 124 days for adult patients (U=2323; p=0.644). The median turn-around time (TAT) of genetic testing was 56 days in pediatric patients and 60 days in adult patients (U=1892; p=0.191). A definitive molecular diagnosis was made in 25/65 (24.6%) of pediatric patients and 9/100 (9%) of adults. Most diagnosed disorders were identified in the categories of immune dysregulation (n=10/25; 40%), antibody deficiencies (n=5/25; 20%), and phagocyte diseases (n=5/25; 20%). Inconclusive outcomes were found in 76/165 (46.1%) patients. Within the patient group with a genetic diagnosis, a change in disease management occurred in 76% of patients.ConclusionIn this cohort, the highest yields of NGS based evaluation for IEI early in the diagnostic trajectory were found in pediatric patients, and in the disease categories immune dysregulation and phagocyte diseases. In cases where a definitive diagnosis was made, this led to important disease management implications in a large majority of patients. More research is needed to establish a uniform diagnostic pathway for cases with inconclusive diagnoses, including variants of unknown significance.

The immune system recognizes and attacks non-self antigens, making up the cornerstone of immunity activity against infection. However, during organ transplantation, the immune system also attacks transplanted organs and leads to immune rejection and transplantation failure. Interestingly, although the embryo and placenta are semi-allografts, like transplanted organs, they can induce maternal tolerance and be free of a vigorous immune response. Also, embryo or placenta-related antibodies might adversely affect subsequent organ transplantation despite the immune tolerance during pregnancy. Therefore, the balance between the immune tolerance in maternal-fetal interface and normal infection defense provides a possible desensitization and tolerance strategy to improve transplantation outcomes. A few studies on mechanisms and clinical applications have been performed to explore the relationship between maternal-fetal immune tolerance and organ transplantation. However, up to now, the mechanisms underlying maternal-fetal immune tolerance remain vague. In this review, we provide an overview on the current understanding of immune tolerance mechanisms underlying the maternal-fetal interface, summarize the interconnection between immune tolerance and organ transplantation, and describe the adverse effect of pregnancy alloimmunization on organ transplantation.

Circular RNAs (circRNAs) represent a novel class of widespread and diverse endogenous RNA molecules. This unusual class of RNA species is generated by a back-splicing event of exons or introns, resulting in a covalently closed circRNA molecule. Accumulating evidence indicates that circRNA plays an important role in the biological functions of a network of competing endogenous RNA (ceRNA). CircRNAs can competitively bind to miRNAs and abolish the suppressive effect of miRNAs on target RNAs, thus regulating gene expression at the posttranscriptional level. The role of circRNAs as ceRNAs in the pathogenesis of cardiovascular and cerebrovascular diseases (CVDs) has been recently reported and highlighted. Understanding the underlying molecular mechanism could aid the discovery of therapeutic targets or strategies against CVDs. Here, we review the progress in studying the role of circRNAs as ceRNAs in CVDs, with emphasis on the molecular mechanism, and discuss future directions and possible clinical implications.

The immune system recognizes and attacks non-self antigens, making up the cornerstone of immunity activity against infection. However, during organ transplantation, the immune system also attacks transplanted organs and leads to immune rejection and transplantation failure. Interestingly, although the embryo and placenta are semi-allografts, like transplanted organs, they can induce maternal tolerance and be free of a vigorous immune response. Also, embryo or placenta-related antibodies might adversely affect subsequent organ transplantation despite the immune tolerance during pregnancy. Therefore, the balance between the immune tolerance in maternal-fetal interface and normal infection defense provides a possible desensitization and tolerance strategy to improve transplantation outcomes. A few studies on mechanisms and clinical applications have been performed to explore the relationship between maternal-fetal immune tolerance and organ transplantation. However, up to now, the mechanisms underlying maternal-fetal immune tolerance remain vague. In this review, we provide an overview on the current understanding of immune tolerance mechanisms underlying the maternal-fetal interface, summarize the interconnection between immune tolerance and organ transplantation, and describe the adverse effect of pregnancy alloimmunization on organ transplantation. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the fourth leading cause of cancer deaths worldwide, with poor prognosis mainly related to metastasis. Fibronectin (FN), a vital component of the extracellular matrix (ECM), has been found involved in tumorigenesis and malignant progression in different types of malignancy. Numerous studies have indicated the distinct expression of FN in various cancers and demonstrated the different functions of FN in the proliferation, migration, and invasion of cancers. Meanwhile, FN isoforms have been extensively used for targeted drug delivery and imaging for tumors. Although a growing number of studies on FN in CRC have been reported, integrated reviews on the relationship between FN and CRC are rare. In this review, we will summarize the association between FN and CRC, including the signaling pathways and molecules involved in, as well as potential diagnostic and therapeutic values of FN for patients with CRC. [ABSTRACT FROM AUTHOR]

Abstract Background In a time of increasing concerns over personalized and precision treatment in breast cancer (BC), filtering prognostic factors attracts more attention. Apoptosis-Inducing Factor Mitochondrion-associated 3 (AIFM3) is widely expressed in various tissues and aberrantly expressed in several cancers. However, clinical implication of AIFM3 has not been reported in BC. The aim of the study is to investigate the crystal structure, clinical and prognostic implications of AIFM3 in BC. Methods AIFM3 expression in 151 BC samples were assessed by immunohistochemistry (IHC). The Cancer Genome Atlas (TCGA) and Kaplan-Meier survival analysis were used to demonstrate expression and survival of AIFM3 signature. Gene Set Enrichment Analysis (GSEA) was performed to investigate the mechanisms related to AIFM3 expression in BC. Results AIFM3 was significantly more expressed in breast cancer tissues than in normal tissues. AIFM3 expression had a significant association with tumor size, lymph node metastasis, TNM stage and molecular typing. Higher AIFM3 expression was related to a shorter overall survival (OS) and disease-free survival (DFS). Lymph node metastasis and TNM stage were independent factors of AIFM3 expression. The study presented the crystal structure of AIFM3 successfully and predicted several binding sites when AIFM3 bonded to PTPN12 by Molecular Operating Environment software (MOE). Conclusions AIFM3 might be a potential biomarker for predicting prognosis in BC, adding to growing evidence that AIFM3 might interact with PTPN12.

Background: The worldwide spread of SARS-CoV-2 has infected millions of people leading to over 0.3 million mortalities. The disruption of sodium homeostasis, tends to be a common occurrence in patients with COVID-19. Methods and results: A total of 1,254 COVID-19 patients comprising 124 (9.9%) hyponatremic patients (under 135 mmol/L) and 30 (2.4%) hypernatremic patients (over 145 mmol/L) from three hospitals in Hubei, China, were enrolled in the study. The relationships between sodium balance disorders in COVID-19 patients, its clinical features, implications, and the underlying causes were presented. Hyponatremia patients were observed to be elderly, had more comorbidities, with severe pneumonic chest radiographic findings. They were also more likely to have a fever, nausea, higher leukocyte and neutrophils count, and a high sensitivity C-reactive protein (HS-CRP). Compared to normonatremia patients, renal insufficiency was common in both hyponatremia and hypernatremia patients. In addition, hyponatremia patients required extensive treatment with oxygen, antibiotics, and corticosteroids. The only significant differences between the hypernatremia and normonatremia patients were laboratory findings and clinical complications, and patients with hypernatremia were more likely to use traditional Chinese medicine for treatment compared to normonatremia patients. This study indicates that severity of the disease, the length of stay in the hospital of surviving patients, and mortality were higher among COVID-19 patients with sodium balance disorders. Conclusion: Sodium balance disorder, particularly hyponatremia, is a common condition among hospitalized patients with COVID-19 in Hubei, China, and it is associated with a higher risk of severe illness and increased in-hospital mortality. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most disseminated diseases across the globe engaging the digestive system. Various therapeutic methods from traditional to the state-of-the-art ones have been applied in CRC patients, however, the attempts have been unfortunate to lead to a definite cure. MiRNAs are a smart group of non-coding RNAs having the capabilities of regulating and controlling coding genes. By utilizing this stock-in-trade biomolecules, not only disease’s symptoms can be eliminated, there may also be a good chance for the complete cure of the disease in the near future. Herein, we provide a comprehensive review delineating the therapeutic relationship between miRNAs and CRC. To this, various clinical aspects of miRNAs which act as a tumor suppressor and/or an oncogene, their underlying cellular processes and clinical outcomes, and, in particular, their effects and expression level changes in patients treated with chemo- and radiotherapy are discussed. Finally, based on the results deducted from scientific research studies, therapeutic opportunities based on targeting/utilizing miRNAs in the preclinical as well as clinical settings are highlighted. [ABSTRACT FROM AUTHOR]

Abstract Background Circular RNAs are a new class of endogenous non-coding RNA that can function as crucial regulators of diverse cellular processes. The diverse types of circular RNAs with varying cytogenetics in cancer have also been reported. Main body of the abstract Circular RNAs can act as a microRNA sponge or through other mechanisms to regulate gene expression as either tumor inhibitors or accelerators, suggesting that circular RNAs can serve as newly developed biomarkers with clinic implications. Here, we summerized recent advances on circular RNAs in cancer and described a circular RNA network associated with tumorigenesis. The clinical implications of circular RNAs in cancer were also discussed in this paper. Short conclusion Growing evidence has revealed the crucial regulatory roles of circular RNAs in cancer and the elucidation of functional mechanisms involving circular RNAs would be helpful to construct a circRNA-miRNA-mRNA regulatory network. Moreover, circular RNAs can be easily detected due to their relative stability, widespread expression, and abundance in exosomes, blood and saliva; thus, circular RNAs have potential as new and ideal clinical biomarkers in cancer.

Keywords: cardiovascular diseases; clinical implication; diabetes mellitus; multidisciplinary management; non-alcoholic fatty liver disease EN cardiovascular diseases clinical implication diabetes mellitus multidisciplinary management non-alcoholic fatty liver disease 680 682 3 12/22/21 20211201 NES 211201 Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease triggered by individual genetic susceptibility and metabolic dysfunction, presenting as hepatic steatosis that affects more than 5% of hepatocytes in the absence of secondary steatosis (eg, excessive alcohol consumption or steatogenic medications). Non-alcoholic fatty liver disease to metabolic dysfunction-associated fatty liver disease: conceptual changes for clinicians, researchers and patients. Cardiovascular diseases, diabetes mellitus, clinical implication, multidisciplinary management, non-alcoholic fatty liver disease. [Extracted from the article]

MicroRNAs (miRNAs) are non-coding small RNA molecules that regulate gene expression at the post-transcriptional/translational level. They act a considerable role not only in the normal progress of development but also in aberrant human diseases, including malignancy. With accumulating proofs of miR-105, the complex role of miR-105 during cancer initiation and progression is gradually emerging. miR-105 acts as a tumor suppressor by inhibiting tumor growth and metastasis or as an oncogene by promoting tumor initiation and invasion, depending on particular tumor contexts and base-pairing genes. In this review, we emphasize the characteristics of miR-105 in cancer to elucidate various deadly tumors and discuss transcriptional regulations that may explain fluctuations in miR-105 expression. This review may provide new ideas for applying miR-105 as a diagnostic and prognostic biomarker.