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The cellular process responsible for the degradation of cytosolic proteins and subcellular organelles in lysosomes was termed "autophagy." This process occurs at a basal level in most tissues as part of tissue homeostasis that redounds to the regular turnover of components inside cytoplasm. The breakthrough in the autophagy field is the identification of key players in the autophagy pathway, compounded under the name "autophagy-related genes" (ATG) encoding for autophagy effector proteins. Generally, the function of autophagy can be classified into two divisions: intracellular clearance of defective macromolecules and organelles and generation of degradation products. Therapeutic strategies using stem cell-based approach come as a promising therapy and develop rapidly recently as stem cells have high self-renewability and differentiation capability as known as mesenchymal stem cells (MSCs). They are defined as adherent fibroblast-like population with the abilities to self-renew and multi-lineage differentiate into osteogenic, adipogenic, and chondrogenic lineage cells. To date, they are the most extensively applied adult stem cells in clinical trials. The properties of MSCs, such as immunomodulation, neuroprotection, and tissue repair pertaining to cell differentiation, processes to replace lost, or damaged cells, for aiding cell repair and revival. Autophagy has been viewed as a remarkable mechanism for maintaining homeostasis, ensuring the adequate function and survival of long-lived stem cells. In addition, authophagy also plays a remarkable role in protecting stem cells against cellular stress when the stem cell regenerative capacity is harmed in aging and cellular degeneration. Understanding the under-explored mechanisms of MSC actions and expanding the spectrum of their clinical applications may improve the utility of the MSC-based therapeutic approach in the future. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is a type of malignancy characterized by high relapse and recurrence rates in the late stage despite optimal surgical intervention and postoperative chemoradiotherapy. Because the management of relapse following definitive treatment is challenging, accurate risk stratification is of clinical significance to improve treatment outcomes. Circular RNAs (circRNAs) are noncoding RNAs featured with cell-type specificity and high stability, owing to their circular structure, making these molecules excellent biomarkers for a variety of diseases. Methods: The levels of hsa_circ_0000190 and 0001649 in plasma samples from 30 healthy controls and 66 OSCC patients were determined by droplet digital polymerase chain reaction. The same primer sets were used with PCR to examine the expression of these two circRNAs in cancerous and adjacent normal tissues. A receiver operating characteristics curve was generated to evaluate the diagnostic value. The Kaplan-Meier method with a log-rank test was used for survival analysis. Results: We identified two circRNAs as potential biomarkers for OSCC, showing that the plasma level of hsa_circ_0000190 was significantly decreased in the late stage and marginally correlated with the development of second primary OSCC. We also found that the decreased plasma hsa_circ_0001649 was correlated with the recurrence and poor prognosis of patients. Additionally, we found that high plasma hsa_circ_0000190, but not hsa_circ_0001649, possibly predicted a better response of patients to induction chemotherapy. Conclusion: Our study demonstrated the potential of biomarkers in plasma to inform not just the tumor but the entire oral cavity, thereby offering a prediction for early recurrence and second primary OSCC. The plasma circRNAs remain valuable for OSCC, albeit the easy accessibility to the oral cavity. [ABSTRACT FROM AUTHOR]

The Omicron variant BA.2 is the dominant form of the severe acute respiratory syndrome coronavirus 2 (SARS- N CoV-2) outbreak in many countries, including those that have already implemented the strictest quarantine mandates that effectively contained the spread of the previous variants. Although many individuals were partially or fully vaccinated, confirmed Omicron infections have far surpassed all other variants combined in just a couple of months since the Omicron variant emerged. The ChAdOx1-S (AstraZeneca), BNT162b2 (Pfizer-BioNTech), and mRNA-1273 (Moderna) vaccines offer protection against the severe illness of SARS-CoV-2 infection; however, these currently available vaccines are less effective in terms of preventing Omicron infections. As a result, a booster dose of BNT162b2 or mRNA-1273 is recommended for individuals >12 years old who had received their second dose of the approved vaccines for >5 months. Herein, we review the studies that assessed the clinical benefits of the booster dose of vaccines against Omicron infections. We also analyzed public data to address whether early booster vaccination effectively prevented the surge of the Omicron infections. Finally, we discuss the consideration of a fourth dose of vaccine as a way to prevent possible upcoming infections. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) ranks many tasks in clinical oncology due to possibly developing a general tumor in men and, usually lead to malignant to death within years. Researches had reported about major factors for being HCC was male sex and HCC associated with cirrhosis in childhood was found more common in males than females. In certain mouse strains as studied, breeding with testosterone significantly increases the development of HCC. Furthermore, castration of male mice diminished the frequency of the development of liver tumors. Meanwhile male hepatitis B virus transgenic mice have a greater occurrence of HCC than females. Methods: We apply degenerate priming PCR to observe the expression of various steroid receptors in livers. Yeast-two hybrid screening to search a novel RNA fragment helps to find a new full-length gene by RACE experiment. RT-PCR is applied to detect various expressions in tissues and cell lines. In situ hybridization detects DNA in Chromosome mapping. GFP-constructs transfection proves the gene localization in cells. Immunoprecipitation pulldown assay verifies protein interaction. Gene transfection followed with luciferase assay demonstrates the interaction of genes within cellular signaling. Genomic alignment analysis for observing sequences data perform from NCBI database website (http://www.ncbi.nim.nih.gov/genebank/). Results: The androgen receptor (AR) expression level is found at the highest level among the steroid receptors families detected in liver tumors. By yeast-two hybrid screening, we cloned an Androgen Receptor Complex Associated Protein (ARCAP), of 95 Kd in molecular weight and its cDNA. ARCAP locates at Chromosome 1. Our findings indicate ARCAP is highly expressed in hepatoma cell lines and liver tumors and their adjacent tumors as observed. Yeast two-hybrid assay and in vitro immunoprecipitation assays demonstrated an interaction between AR and ARCAP. Conclusion: We aim to search for different types and levels of steroid receptors expressed within human HCCs and in the adjacent liver tissues. To verify possible molecular mechanisms by which AR might affect hepatoma cells, we had characterized a novel protein ARCAP which functions as a coregulator to interact with AR within liver. The ligand-dependent AR with its cofactor, ARCAP, can induce a signal cascade by transactivation. [ABSTRACT FROM AUTHOR]

Background: Plate and locked intramedullary nailing for humeral fractures are golden standard procedure, but the humerus is a nonweight-bearing bone and can tolerate a larger range of acceptable alignment. We believe the elastic stable intramedullary nails (ESINs) can provide enough relative stability for humeral shaft fractures in certain adult patients. Methods: There are four new indications for using ESINs: (1) patient could not tolerate a sugar-tong splint but was a high risk for general anesthesia, (2) intramedullary canal narrowing (<7 mm), (3) long spiral or oblique fracture over the metadiaphyseal junction, and (4) obesity. All patients received retrograde fixation with two titanium elastic nails, except for one patient with a long spiral fracture over the proximal metadiaphysis. Patients had routine follow-up plain radiographs until bone union, and we evaluated functional results of patients by Mayo Elbow Performance Score and asked to complete Quick Disabilities of the Arm, Shoulder and Hand score at the last outpatient clinic visit. Results: A total of 16 patients with a mean age of 54.4 years were included. The mean follow-up time was 14 ± 2.5 months, and the average time to bone union was 16 ± 4.3 weeks. There were no wound infections, loss of reduction, fracture nonunion, implant failure, or skin irritation expect for one nail back-out because of osteoporosis. Conclusion: We have reported good results using ESINs for the displaced fractures of the humerus in the four indication adults who would not be able to tolerate plate fixation or intramedullary nailing. The ESINs fixation method is a simple procedure that provides a small incision, minimal blood loss, short surgical time, and relative stability fixation. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most prevalent human cancers, and single-cell RNA sequencing (scRNA-seq) has been widely used to study human lung cancer at the cellular, genetic, and molecular level. Even though there are published reviews, which summarized the applications of scRNA-seq in human cancers like breast cancer, there is lack of a comprehensive review, which could effectively highlight the broad use of scRNA-seq in studying lung cancer. This review, therefore, was aimed to summarize the various applications of scRNA-seq in human lung cancer research based on the findings from different published in vitro, in vivo, and clinical studies. The review would first briefly outline the concept and principle of scRNA-seq, followed by the discussion on the applications of scRNA-seq in studying human lung cancer. Finally, the challenges faced when using scRNA-seq to study human lung cancer would be discussed, and the potential applications and challenges of scRNA-seq to facilitate the development of personalized cancer therapy in the future would be explored. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues the pandemic spread of the coronavirus disease 2019 (COVID-19), over 60 million people confirmed infected and at least 1.8 million dead. One of the most known features of this RNA virus is its easiness to be mutated. In late 2020, almost no region of this SARS-CoV-2 genome can be found completely conserved within the original Wuhan coronavirus. Any information of the SARS-CoV-2 variants emerged through as time being will be evaluated for diagnosis, treatment, and prevention of COVID-19. Methods: We extracted more than two million data of SARS-CoV-2 infected patients from the open COVID-19 dashboard. The sequences of the 38-amino acid putative open reading frame 10 (Orf10) protein within infected patients were gathered output through from National Center for Biotechnology Information and the mutation rates in each position were analyzed and presented in each month of 2020. The mutation rates of A8 and V30 within Orf10 are displayed in selected counties: United States, India, German, and Japan. Results: The numbers of COVID-19 patients are correlated to the death numbers, but not with the death rates (stable and <3%). The amino acid positions locating at A8(F/G/L), I13, and V30(L) within the Orf10 sequence stay the highest mutation rate; N5, N25, and N36 rank at the lowest one. A8F expressed highly dominant in Japan (over 80%) and German (around 40%) coming to the end of 2020, but no significant finding in other countries. Conclusion: The results demonstrate via mutation analysis of Orf10 can be further combined with advanced tools such as molecular simulation, artificial intelligence, and biosensors that can practically revealed for protein interactions and thus to imply the authentic Orf10 function of SARS-CoV-2 in the future. [ABSTRACT FROM AUTHOR]

Background: Various upper limb activities were speculated to be associated with the development of carpal tunnel syndrome (CTS). Nonetheless, there are currently no standardization on the uses of parameters in CTS assessments, nor are there any conclusive findings regarding the usefulness of various sonographic measurements in studies of different upper limb activities. In this review, we intend to evaluate the methodology of assessing CTS induced by upper limb activities with ultrasonographic technique and provide corresponding suggestions. Methods: Clinical studies on the association between upper limb activities and prevalence of CTS using ultrasonography were recruited in a database research on the basis of a procedural selection criteria and reviewed. The following qualitative items were extracted: characteristics of studies, scanning methods, selection of sonographic parameters, and related article findings. Results: Eleven studies were qualified for this review. Three studies were computer keyboard typing related, five studies were electronic device related, and three studies were wheelchair-related. All sampled articles included cross-sectional area (CSA) at the pisiform level. The swelling ratio (SR) and flattening ratio (FR) at the hamate level are also used in most studies in addition to the CSA at the pisiform level. The effectiveness of such parameters is subjected to various confounding factors such as age, weight, body mass index, and wrist anthropometrics, suggesting CSA and SR with sufficient levels had significant values as sonographic parameters. Values of parameters were found affecting symptomatic signs and hand dominance. Conclusion: Ultrasound scan is a suitable tool to assess the relationship between upper limb activity and CTS. CSA at the pisiform level and SR and the FR at the hamate levels are generally suitable in upper limb-associated CTS investigations. Specific study designs are required to eliminate different confounding factors accordingly. [ABSTRACT FROM AUTHOR]

Background: Gene therapy is the advanced therapeutics for supplying or replacing the genetic material in patients with inherited disorders. Recent clinical studies have made some progress in a wide range of applications, including monogenic disorders, neurodegenerative diseases, malignant tumors, and congenital diseases. Heart diseases, especially myocardial ischemia, remain one of the leading causes of mortality worldwide and usually result in irreparable cardiomyocyte damage and severe heart failure. Methods: Most advances in induced pluripotent stem cell (iPSC) technologies for promoting regenerative medicine and stem cell research. However, the driver molecules of myocardial-lineage differentiation and the functional reconstruction capacity of iPSC-derived cardiomyocytes are still an open question. Nanomedicine-based gene delivery provided a crucial platform to carry on the biogenomic materials for equipping functionalities and engineering the living organ environment. Nanodiamond (ND), a carbon-based nanomaterial, has been discovered and shown the high biocompatible and less toxicity for transporting protein, drug, and genomic plasmids. Results: Here, we applied ND as a gene delivery vehicle to carry microRNA (miR-181a), and then transfected into iPS to promote cardiomyocyte-lineage differentiation. Notably, miR-181a plays a key role in iPS-derived cardiomyocyte differentiation which directly targets Hox-A11, leading to elevated MyoD expression and enhanced cardiomyocyte differentiation. Conclusion: Our study demonstrated that miR-181a promotes iPSC differentiation into functional cardiomyocytes. Delivery of NANO-DIAMOND-miR-181a may host clinical potential to enhance the differentiation and recovery of the cardiogenic function in injured cardiomyocytes. [ABSTRACT FROM AUTHOR]

Background: Cardiotocography is a common method of electronic fetal monitoring (EFM) for fetal well-being. Data-driven analyses have shown potential for automated EFM assessment. For this preliminary study, we used a novel artificial intelligence method based on fully convolutional networks (FCNs), with deep learning for EFM evaluation and correct recognition, and its possible role in evaluation of nonreassuring fetal status. Methods: We retrospectively collected 3239 EFM labor records from 292 deliveries and neonatal Apgar scores between December 2018 and July 2019 at a single medical center. We analyzed these data using an FCN model and compared the results with clinical practice. Results: The FCN model recognized EFM traces like physicians, with an average Cohen's kappa coefficient of agreement of 0.525 and average area under the receiver operating characteristic curve of 0.892 for six fetal heart rate (FHR) categories. The FCN model showed higher sensitivity for predicting fetal compromise (0.528 vs 0.132) but a higher false-positive rate (0.632 vs 0.012) compared with clinical practice. Conclusion: FCN is a modern technique that may be useful for EFM trace recognition based on its multiconvolutional layered analysis. Our model showed a competitive ability to identify FHR patterns and the potential for evaluation of nonreassuring fetal status. [ABSTRACT FROM AUTHOR]

The pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has brought an unprecedented impact upon the global economy and public health. Although the SARS-CoV-2 virology has been gradually investigated, measures to combat this new threat in public health are still absent. To date, no certificated drug or vaccine has been developed for the treatment or prevention of coronavirus disease Extensive researches and international coordination has been conducted to rapidly develop novel vaccines against SARS-CoV-2 pandemic. Several major breakthroughs have been made through the identification of the genetic sequence and structural/non-structural proteins of SARS-CoV-2, which enabled the development of RNA-, DNA-based vaccines, subunit vaccines, and attenuated viral vaccines. In this review article, we present an overview of the recent advances of SARS-CoV-2 vaccines and the challenges that may be encountered in the development process, highlighting the advantages and disadvantages of these approaches that may help in effectively countering COVID-19. [ABSTRACT FROM AUTHOR]

X-linked juvenile retinoschisis (XLRS) is one of the common early-onset hereditary retinal degenerative diseases in men. The common symptoms of XLRS range from mild to severe central vision loss and radial stripes created by the fovea, the division of the inner layer of the retina in the peripheral retina and the significant decrease in b-wave amplitude (ERG). Retinoschisin, the 224-amino-acid protein product of the retinoschisis 1 (RS1) gene, contains a discoid domain as the primary structural unit, an N-terminal cleavable signal sequence, and an oligomerization-area component. Retinoschisin is a homo-octamer complex with disulfide links that are released by retinal cells. It helps preserve the retina's integrity by binding to the surface of photoreceptors and bipolar cells. As a recessive genetic disease, XLRS was usually treated by prescribing low vision aids in most clinical cases. A gene replacement therapy based on adeno-associated virus vectors was initiated and showed a breakthrough in treating XLRS in 2014. Understanding the revolution of gene therapy for treating XLRS may accelerate its development and make this gene therapy the template for developing therapeutics against other inherited retinal diseases. [ABSTRACT FROM AUTHOR]

Background: Age-related macular degeneration (AMD) is one of the leading causes of vision loss. Once the retinal pigment epithelium (RPE) layers are destroyed, the poor visual acuity and recognition are generally irreversible. Cell therapy that possesses enormous potential in regenerative medicine may provide an alternative treatment for several incurable diseases such as AMD. In this study, we developed an innovative polydimethylsiloxane (PDMS)-based biomimetic scaffolds with cylinder micropillars for the cultivation of induced pluripotent stem cell--derived RPEs (iPSC-RPEs). RPEs were cultured on the PDMS-based biomimetic scaffolds and validated the cells gene expression. Methods: The biomimetic PDMS scaffold was fabricated through spin coating and lithography method. It was further modified on surface with biomolecules to improve cell affinity and stability. The iPSC-RPEs were seeded on the scaffold and analyzed with characteristic gene expression. Results: PDMS biomimetic scaffold was analyzed with Fourier transform infrared spectroscopy and proved its chemical composition. iPSC-RPEs demonstrated confluent cell monolayer on the scaffold and maintained RPE-specific gene expression, which proved the PDMS-based biomimetic scaffold to be supportive for iPSC-RPEs growth. Conclusion: The PDMS interface allowed regular growth of iPSC-RPEs and the design of cylinder micropillars further provided the bioscaffold high motion resistance may improve the engraftment stability of iPSC-RPEs after transplantation. Taken together, this innovative PDMS-based biomimetic scaffold may serve as an ideal interface for in vitro iPSC-RPE cultivation and subsequent transplantation in vivo. This novel device exhibits better bioavailability than conventional injection of donor cells and may be an alternative option for the treatment of AMD. [ABSTRACT FROM AUTHOR]

Background: Heart diseases, especially myocardial ischemia, remain one of the leading causes of mortality worldwide and usually result in irreparable cardiomyocyte damage and severe heart failure. Recent advances in induced pluripotent stem cell (iPSC) technologies for applied regenerative medicine and stem cell research, especially for iPSC-derived cardiomyocytes have increased the hope for heart repair. However, the driver molecules of myocardial differentiation and the functional reconstruction capacity of iPSC-derived cardiomyocytes are still questionable. Methods: Herein, we established a rapid differentiated platform that is involved in cardiomyogenic differentiation and maturation from iPSCs in vitro. Functional analysis is performed in miR-181a-transfected iPSC-derived cardiomyocyte (iPSC-cardio/miR-181a) under a time-lapse microscope. In addition, we calculated the beating area and frequency of iPSC-cardio/miR-181a cells in the presence of HCN4 shRNA or miR-181a SPONGE. Results: miR-181a enhanced the beating area and maintained the beating frequency of iPSC-derived cardiomyocytes by enhancing HCN4 expression. Conclusion: miR-181a would play a key role on maintaining proper beating function in iPSC-derived cardiomyocytes. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a common degenerative disease; however, its exact pathophysiology and early diagnosis are still a challenge. Growing attention to the exosomes may inspire innovations that would make the current management of OA more effective. The exosomes in synovial fluid are relatively stable, and they can be easily isolated by the relatively noninvasive procedure of liquid biopsy to provide diagnostic and monitoring value. Some miRNAs (miR-504, miR-146a, miR-26a, miR-200c, and miR-210) have been known to be secreted in exosomes of OA patients. On the other hand, intraarticular injection of platelet-rich plasma (PRP) is becoming a popular therapy for OA patients. PRP is also a source of exosomes and their numerous contents. It is evident from the literature that PRP-derived exosomes can induce chondrogenic gene expression in OA chondrocytes. Here, we review the latest findings on the roles of exosomes in OA with the emphasis on PRP-derived exosomes and their potential applications for treating OA. [ABSTRACT FROM AUTHOR]

The liver is an essential organ that is primarily responsible for digestion and eliminating toxic substances from the body. After the industrial revolution, Western diet and lifestyle changes have increased the incidence of several liver diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). NAFLD and NASH are mostly asymptomatic at early stages, and the disease progression from NAFLD to life-threatening HCC remains not fully understood. Circular RNA (circRNA) is consist of a circular structure, and the circRNA-microRNA(miRNA)-mRNA axes have been shown to be involved in several cellular events, including apoptosis, vascularization, metastasis, etc. The highly stable structure of circRNAs has enabled themselves to be used as putative biomarkers of several diseases. Here, we conducted a literature review and discussed the identified roles of circRNAs in NAFLD, NASH, liver cirrhosis, and HCC. For example, deficiency of circRNA_0046366 and circRNA_0046367 has been shown as the characteristics of NAFLD, and restoration of these circRNAs ameliorates the oxidative stress, lipotoxicity, and disease severity in NAFLD. Silencing of circ_0071410 was shown to alleviate hepatic stellate activation, the key step of liver cirrhosis. CDR1 and circ_0067934 can facilitate the invasion and metastasis of HCC, while circMTO1 negatively regulates the progression of HCC. Although several research works have been conducted, the whole picture of circRNA-related underlying mechanisms is unclear. Future works using high-throughput bioinformatic approaches will be needed to delineate the role of circRNAs in liver diseases and to further develop novel diagnostics and therapeutics. [ABSTRACT FROM AUTHOR]