Endoplasmic reticulum stress response pathway-mediated cell death in ovarian cancer.

The endoplasmic reticulum (ER) is one of the largest organelles, and Endoplasmic Reticulum Stress Response Pathway is a series of responses triggered by the homeostatic imbalance of the ER and the state in which unfolded or misfolded proteins accumulate in the ER, which can trigger cell death. Cell death plays a crucial role in the development of diseases such as gynecological oncology. Herein, we review the current research on the response and ovarian cancer, discussing the key sensors (IRE1, PERK, ATF6), and the conditions under which it occurs (Ca2+ homeostasis disruption, hypoxia, others). Using the response as a starting point, provide a comprehensive overview of the relationship with the four types of cell death (apoptosis, autophagy, immunogenic cell death, paraptosis) in an attempt to provide new targeted therapeutic strategies for the organelle-Endoplasmic Reticulum Stress Response Pathway-cell death in ovarian cancer therapy.

Future prospect of polysaccharide as a potential therapy in hepatocellular carcinoma: A review.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. HCC almost exclusively develops in patients with chronic liver disease, driven by a vicious cycle of liver injury, inflammation and regeneration that typically spans decades. A variety of new agents are in development for the treatment of the disease. Polysaccharide is important component of higher plants, membrane of the animal cell and the cell wall of microbes. It is also closely related to the physiological functions. Recently, there has been growing interest in polysaccharides as bioactive natural products, particularly in treating HCC. This paper provides a review of recent experimental and clinical studies on the effects and potential applications of polysaccharides in HCC treatment, aiming to offer theoretical insights and inspiration for further research on the bioactivity mechanisms of polysaccharides in HCC treatment.

The Gut Microbiome and Acute Leukemia: Implications for Early Diagnostic and New Therapies.

Acute leukemia (AL), one of the hematological malignancies, shows high heterogeneity. Tremendous progresses are achieved in treating AL with novel targeted drugs and allogeneic hematopoietic stem cell transplantation, there are numerous issues including pathogenesis, early diagnosis, and therapeutic efficacy of AL to be solved. In recent years, an increasing number of studies regarding microbiome have shed more lights on the role of gut microbiota in promoting AL progression. Mechanisms related to the role of gut microbiota in enhancing AL genesis are summarized in the present work, especially on critical pathways like leaky gut, bacterial dysbiosis, microorganism-related molecular patterns, and bacterial metabolites, resulting in AL development. Additionally, the potential of gut microbiota as the biomarker for early AL diagnosis is discussed. It also outlooks therapies targeting gut microbiota for preventing AL development.

Protein acetylation and related potential therapeutic strategies in kidney disease.

Kidney disease can be caused by various internal and external factors that have led to a continual increase in global deaths. Current treatment methods can alleviate but do not markedly prevent disease development. Further research on kidney disease has revealed the crucial function of epigenetics, especially acetylation, in the pathology and physiology of the kidney. Histone acetyltransferases (HATs), histone deacetylases (HDACs), and acetyllysine readers jointly regulate acetylation, thus affecting kidney physiological homoeostasis. Recent studies have shown that acetylation improves mechanisms and pathways involved in various types of nephropathy. The discovery and application of novel inhibitors and activators have further confirmed the important role of acetylation. In this review, we provide insights into the physiological process of acetylation and summarise its specific mechanisms and potential therapeutic effects on renal pathology.

The Gut Microbiome and Autoimmune Hepatitis: Implications for Early Diagnostic Biomarkers and Novel Therapies.

Autoimmune hepatitis (AIH) is a serious chronic liver disease that may last for decades and eventually develop into cirrhosis and liver failure. In recent years, people have paid more attention to the microbiome-gut-liver axis, which provides guidance for all to explore the role of microbiome in the occurrence and development of liver diseases. In this review, the possible mechanism of intestinal microbes promoting the occurrence of AIH, mainly expounding the key ways such as bacterial ecological imbalance, intestinal leakage, and molecular simulation between microbes and autoantigens is summarized. In addition, this paper also discusses that intestinal microbiome has great potential as a biomarker for early diagnosis of AIH, and intestinal microbiome is also a candidate target for prevention and treatment of AIH. Finally, the study summarizes and prospects the targeted therapy of intestinal microorganisms to prevent the occurrence and development of AIH.

Oxidative Stress in Brain in Amnestic Mild Cognitive Impairment.

Amnestic mild cognitive impairment (MCI), arguably the earliest clinical stage of Alzheimer disease (AD), is characterized by normal activities of daily living but with memory issues but no dementia. Oxidative stress, with consequent damaged key proteins and lipids, are prominent even in this early state of AD. This review article outlines oxidative stress in MCI and how this can account for neuronal loss and potential therapeutic strategies to slow progression to AD.

N6-Methyladenosine-Modification-Related Ophthalmic Diseases and Potential Therapeutic Strategies.

The N6-methyladenosine (m6A) is the most abundant internal modification in advanced eukaryotic mRNAs, and it plays an important role in mRNA metabolism and diverse biological processes. Moreover, m6A modification is dynamically reversible and may reshape gene expression patterns after demethylation induced by drug interventions, which may reverse the occurrence and progression of certain diseases. Although the role of changes in DNA methylation in ophthalmic diseases has been well described, the regulatory role of the m6A modification in ophthalmic diseases is still a new field of study. This paper aims to systematically summarize the latest research progress about m6a-modification-related ophthalmic diseases and potential therapeutic strategies. All English literature relevant to our research was searched in PubMed and CNKI databases, using appropriate keywords. Our study reviews the regulatory role of m6A in ophthalmic diseases. It covers almost all of the reported m6A-related ophthalmic diseases and proposes potential treatment strategies for each disease. This review will provide direction for further research on m6A in ophthalmic diseases and help in the treatment of ophthalmic diseases in the future.

Gut microbiota and metabolites in myasthenia gravis: Early diagnostic biomarkers and therapeutic strategies.

Myasthenia gravis (MG) is an acquired neurological autoimmune disorder characterized by dysfunctional transmission at the neuromuscular junction. The complex interplay of genetic and environmental influences is important for the occurrence and development of the disease. Recently, some studies have demonstrated the relationship between gut microbiota dysbiosis and MG. Certain gut microbial strains have been shown to attenuate or promote MG. This review summarized the role of gut microbiota and metabolites in MG progression. Meanwhile, we discuss the important potential of gut microbiota and metabolites for the early diagnostic biomarker of MG. Regulating gut microbiota may be novel and effective treatment for MG. Thus, targeted gut microbiota therapies are discussed and prospected to prevent MG progression.

Mechanism and strategies of immunotherapy resistance in colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer in the world. Although there are standard treatment options for CRC, most patients respond poorly to these treatments. Immunotherapies have gradually emerged due to the increasing awareness and understanding of tumor immunity, exhibiting good therapeutic efficacy in various cancers. Immunotherapies include cytokines, immune checkpoint inhibitors (ICIs), and adoptive cell therapies. In particular, ICIs, which are antibodies against cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), or its ligand PD-L1, have been successfully applied clinically for solid tumors, relieving the inhibitory effect of the tumor microenvironment on T cells. However, only a minority of patients with cancer achieve a durable clinical response during immunotherapy. Several factors restrict the efficacy of immunotherapy, leading to the development of drug resistance. In this review, we aimed to discuss the current status of immunotherapy for CRC and elaborate on the mechanisms that mediate resistance to immunotherapy and other potential therapeutic strategies.

The Gut Microbiome and Hepatocellular Carcinoma: Implications for Early Diagnostic Biomarkers and Novel Therapies.

Hepatocellular carcinoma (HCC) ranks the third place among all causes inducing cancer-associated mortality, worldwide. HCC nearly exclusively occurs in cases suffering from chronic liver disease (CLD), which results from the vicious cycle of liver damage, inflammation, and regeneration possibly lasting for dozens of years. Recently, more and more investigation on microbiome-gut-liver axis enhances our understanding toward how gut microbiota promotes liver disease and even HCC development. In this review, we summarize the mechanisms underlying the effect of gut microbiota on promoting HCC occurrence, with the focus on key pathways such as bacterial dysbiosis, leaky gut, bacterial metabolites, and microorganism-related molecular patterns, which promote liver inflammation, genotoxicity, and fibrosis that finally lead to cancer occurrence. Furthermore, we discuss gut microbiota's important potential to be the early diagnostic biomarker for HCC. Gut microbiota may be the candidate targets to simultaneously prevent CLD and HCC occurrence among advanced liver disease cases. We outlook the gut microbiota-targeting treatments in detail to prevent CLD and HCC progression.

Role of ARK5 in cancer and other diseases (Review).

Malignant tumors are often exposed to hypoxic and glucose-starved microenvironments. AMP-activated protein kinase (AMPK) is an energy sensor that is stimulated during energy-deficient conditions and protects cells from hypoxic injury by regulating metabolism. AMPK-related protein kinase 5 (ARK5) is a member of the catalytic sub-unit of the AMPK family and has an important role in energy regulation and hypoxia. ARK5 is regulated by Akt and liver kinase B1 and is associated with numerous tumor-related molecules to exert the negative effects of tumors. Studies have revealed ARK5 overexpression in cases of tumor invasion and metastasis and a positive association with the degree of cancer cell malignancy, which is regarded as a key element in determining cancer prognosis. Furthermore, ARK5 downregulation improves drug sensitivity through the epithelial-mesenchymal transition pathway, indicating that it may be a potential therapeutic target. In other non-cancer conditions, ARK5 has various roles in neurodegenerative diseases (Alzheimer's and Huntington's disease), renal disorders (diabetic nephropathy and renal fibrosis) and physiological processes (striated muscle generation). In the present review, the upstream and downstream molecular pathways of ARK5 in cancer and other diseases are described and potential therapeutic strategies are discussed.

Genetic heterogeneity and predictive biomarker for pulmonary sarcomatoid carcinomas.

PURPOSE: The aim of this study is to investigate the genetic heterogeneity (carcinomatous vs. sarcomatous components) and predictive biomarkers in patients with pulmonary sarcomatoid carcinoma (PSC). METHODS: Genetic alterations and biomarkers of immunotherapy were performed in a discovery set (n = 6) of PSC. Next-generation sequencing (NGS) on a pan-cancer gene panel was applied to detect the genetic alterations in each component, and the respective mutation profiling and tumor mutation burden (TMB) were compared as well. Immunohistochemistry (IHC) assay with SP263 antibody was used to detect the protein expression of programmed death-ligand 1 (PD-L1) in each component. RESULTS: Comparative genetic analysis revealed that the separate carcinomatous and sarcomatous components shared strikingly common mutations. TP53 (4/6, 66.7%) was the most common genetic alteration in 6 PSC patients. MET exon 14 skipping was detected in one case, accounting for 16.7%. An EZR-ROS1 fusion (EZR: intron10-ROS1: intron32) was identified in one case. The TMB of the two components was similar. Nevertheless, significantly higher PD-L1 expression was found in carcinomatous components compared to sarcomatous components. MDM2 amplification was detected in 2/6 (33.3%) of cases and STK11 mutation in 1/6 (16.7%) of cases. CONCLUSIONS: PSC containing carcinomatous and sarcomatous components had a mild heterogeneity; the two components may evolve from common ancestral cells. High PD-L1 expression suggests that immunotherapy could be used as a potential therapy for PSC patients, while patients with negative immune-responsive genes need to be screened out. Altogether, these findings further highlight that the detection of genetic alteration and PD-L1 expression plays an important role in treatment of patients with PSC.

Potential Therapeutic Strategies of Regenerative Medicine for Renal Failure.

BACKGROUND: Kidney diseases are a public health problem worldwide. Available therapies include function replacement by dialysis or transplant, which are associated with a high morbidity and mortality. Likewise, none of these treatments compensate all kidney functions. There is a great concern in developing more effective therapies with the ability to replace the wide range of renal functions, so that, new studies on developing therapeutic strategies have focused on regenerative medicine. OBJECTIVE: The aim of this paper is to review the new advances in regenerative medicine for renal failure treatment. RESULTS: Regenerative medicine comprises two therapeutic strategies: cell therapy and tissue engineering. Cell therapy techniques depend on cell and tissue cultures, with the aim to replace morphological structures, tissues, and functions. The main strategic strength of cell therapy in renal failure is the incorporation of additional cells in a damaged kidney, for which purpose different kind of Stem Cells (SCs) have been used such as Embryonic SCs, induced Pluripotent SCs, Multipotent SCs, Renal SCs, or drugs that increase survival and mobilization of SCs. Tissue engineering complements cell therapy combining techniques of biological sciences and engineering to create structures and devices as scaffolds, matrices or 3D biocompatible materials. CONCLUSION: Even though there is a significant advance in regenerative medicine strategies, we are far from using any of its techniques on health institutions, due to it is necessary to evaluate side effects, biodistribution, dosage, type of administration, vehicle of cell therapy, as well as the evaluation of response time and long-term studies, among other studies.