Epilepsy is one of the most common brain disorders that not only causes death worldwide, but also affects the daily lives of patients. Previous studies have revealed that inflammation plays an important role in the pathophysiology of epilepsy. Activation of inflammasomes can promote neuroinflammation by boosting the maturation of caspase-1 and the secretion of various inflammatory effectors, including chemokines, interleukins, and tumor necrosis factors. With the in-depth research on the mechanism of inflammasomes in the development of epilepsy, it has been discovered that NLRP3 inflammasomes may induce epilepsy by mediating neuronal inflammatory injury, neuronal loss and blood-brain barrier dysfunction. Therefore, blocking the activation of the NLRP3 inflammasomes may be a new epilepsy treatment strategy. However, the drugs that specifically block NLRP3 inflammasomes assembly has not been approved for clinical use. In this review, the mechanism of how HDACs, an inflammatory regulator, regulates the activation of NLRP3 inflammasome is summarized. It helps to explore the mechanism of the HDAC inhibitors inhibiting brain inflammatory damage so as to provide a potential therapeutic strategy for controlling the development of epilepsy.

BACKGROUND: Diabetic nephropathy is a progressive kidney disease that frequently results in end-stage renal disorders and is characterized by proteinuria, albuminuria, decreased filtration, and renal fibrosis. Despite the fact that there are a number of therapeutic alternatives available, DN continues to be the main contributor to end-stage renal disease. Therefore, significant innovation is required to enhance outcomes in DN patients. MATERIAL AND METHODS: Information was collected from online search engines like, Google Scholar, Web of Science, PubMed, Scopus, and Sci-Hub databases using keywords like diabetes, nephropathy, kidney disease, autophagy, etc. Result: Natural compounds have anti-inflammatory and antioxidant properties and impact various signaling pathways. They ameliorate kidney damage by decreasing oxidative stress, inflammatory process, and fibrosis and enhance the antioxidant system, most likely by activating and deactivating several signaling pathways. This review focuses on the role of metabolic memory and various signaling pathways involved in the pathogenesis of DN and therapeutic approaches available for the management of DN. Special attention is given to the various pathways modulated by the phytoconstituents.

Truly miraculous medications and antibiotics have helped save untold millions of lives. Antibiotic resistance, however, is a significant issue related to health that jeopardizes the effectiveness of antibiotics and could harm everyone's health. Bacteria, not humans or animals, become antibiotic-resistant. Bacteria use quorum-sensing communication routes to manage an assortment of physiological exercises. Quorum sensing is significant for appropriate biofilm development. Antibiotic resistance occurs when bacteria establish a biofilm on a surface, shielding them from the effects of infection-fighting drugs. Acylated homoserine lactones are used as autoinducers by gram-negative microscopic organisms to impart. However, antibiotic resistance among ocular pathogens is increasing worldwide. Bacteria are a significant contributor to ocular infections around the world. Gram-negative microscopic organisms are dangerous to ophthalmic tissues. This review highlights the use of elective drug targets and treatments, for example, combinational treatment, to vanquish antibiotic-resistant bacteria. Also, it briefly portrays anti-biotic resistance brought about by gram-negative bacteria and approaches to overcome resistance with the help of quorum sensing inhibitors and nanotechnology as a promising medication conveyance approach to give insurance of anti-microbials and improve pathways for the administration of inhibitors of quorum sensing with a blend of anti-microbials to explicit target destinations and penetration through biofilms for treatment of ocular infections. It centres on the methodologies to sidestep the confinements of ocular anti-biotic delivery with new visual innovation.

Nicotine, minodronic acid, nicotinamide (niacin), zolpidem, zolimidine, and other pyridine-based chemicals play vital roles in medicine and biology. Pyridine-containing drugs are widely available on the market to treat a wide range of human ailments. As a result of these advances, pyridine research is continually expanding, and there are now higher expectations for how it may aid in the treatment of numerous ailments. This evaluation incorporates data acquired from sources, like PubMed, to provide a thorough summary of the approved drugs and bioactivity data for compounds containing pyridine. Most of the reactions discussed in this article will provide readers with a deeper understanding of various pyridine-related examples, which is necessary for the creation of copper catalysis-based synthetic processes that are more accessible, secure, environmentally friendly, and practical, and that also have higher accuracy and selectivity. This paper also discusses significant innovations in the multi-component copper-catalyzed synthesis of N-heterocycles (pyridine), with the aim of developing precise, cost-effective, and environmentally friendly oxygenation and oxidation synthetic methods for the future synthesis of additional novel pyridine base analogs. Therefore, the review article will serve as a novel platform for researchers investigating copper-based pyridine compounds.

Alzheimer's disease (AD) is an age-dependent neurodegenerative disorder and the leading cause of dementia. AD is characterized by the aggregation of amyloid-ß (Aß) peptide, increased levels of tau protein, and loss of redox homeostasis responsible for mitochondrial dysfunction, oxidative stress, and neuroinflammation. Excessive accumulation of toxic Aß plaques activates microglia, which initiates neuroinflammation and consequently accelerates synaptic damage and neuronal loss. Various proinflammatory cytokines release, microglia proliferation, reactive astrocyte, and oxidative (reactive oxygen species (ROS) production, level of antioxidant enzymes, redox homeostasis, and lipid peroxidation) stress play a major role in AD. Several studies revealed that nuclear factor erythroid 2-related factor 2 (Nrf2) regulates redox homeostasis and works as an anti-inflammatory in various neurodegenerative disorders. D-Glutamate expression of transcription factor Nrf2 and its genes (glutamate-cysteine ligase catalytic subunit (GCLC), Heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase I (NQO1)) has been found in AD. Nrf2-HO-1 enhances the expression of antioxidant genes, inhibits microglia-mediated inflammation, and boosts mitochondrial function, suggesting that modulators of this protein may be useful to manage AD. This review focuses on the role of Nrf2 in AD, with a particular emphasis on the various pathways involved in the positive and negative modulation of Nrf2, namely Phosphoinositide 3-kinase (PI3K), Glycogen synthase kinase-3 (GSK-3), Nuclear factor kappa-B (NF-κB), and p38Mitogen-activated protein kinases (p38MAPK). Also, we have discussed the progress and challenges regarding the Nrf2 activators for AD treatment.

BACKGROUND: Several signaling pathways are involved in the process of angiogenesis, which is one of the most important hallmarks of glioblastoma multiforme (GBM). Identifying related gene variants can help researchers work out what causes anti-angiogenesis drug resistance. OBJECTIVE: The goal of this systematic analysis was to identify all mutations and polymorphisms involved in angiogenesis pathways in GBM and their impact on clinical outcomes. METHODS: The keywords include glioblastoma, angiogenesis, signaling pathway, mutation, polymorphism, and related terms used to search ISI, PubMed, and Scopus for relevant articles published up to January 2022. The PRISMA protocol was used to conduct our systematic review. The related articles were taken into consideration. The risk of bias in the associated articles was surveyed, as well as the article scoring. Two authors collaborated on data extraction. RESULTS: The inclusion criteria were included in 32 articles out of a total of 787 articles. VEGF, HIF1a, EGFR, PI3K, and MAPK are the pathways that have been studied the most. IDH1, VEGF, VEGFR, EGFR, and HIF1a are the genes with the highest frequency of mutations or polymorphisms. CONCLUSION: In conclusion, this study found that angiogenesis in primary or recurrent GBM is linked to gene changes in eleven signaling pathways. However, some of these gene mutations have been researched numerous times in relation to angiogenesis, while others have only been studied once. Understanding these changes will help us employ combination therapies more effectively for GBM patients' survival and personal medicine.

Cancer is a persistent and urgent health problem that affects the entire world. Not long ago, regulatory biomolecules referred to as long noncoding RNAs (lncRNAs) might have value for their innate abundance and stability. These single-stranded RNAs potentially interfere with several physiological and biochemical cellular processes involved in many human pathological situations, particularly cancer diseases. Ferritin heavy chain1 pseudogene 3 (FTH1P3), a lncRNA that is ubiquitously transcribed and belongs to the ferritin heavy chain (FHC) family, represents a novel class of lncRNAs primarily found in oral squamous cell carcinoma. Further research has shown that FTH1P3 is involved in other malignancies such as uveal melanoma, glioma, esophageal squamous cell carcinoma, non-small cell lung cancer, breast cancer, laryngeal squamous cell carcinoma, and cervical cancer. Accordingly, FTH1P3 significantly enhances cancer symptoms, including cell proliferation, invasion, metastasis, chemoresistance, and inhibition of apoptosis through many specific mechanisms. Notably, the clinical data significantly demonstrated the association of FTH1P3 overexpression with poor prognosis and poor overall survival within the examined samples. Here, we summarize all the research published to date (13 articles) on FTH1P3, focusing on the biological function underlying the regulatory mechanism and its possible clinical relevance.

Bladder cancer (BC) is one of the most common malignant tumors worldwide and poses a significant hazard to human health. During the development of BC, hypoxia plays a crucial role. Hypoxia-inducible factor (HIF) is a key transcription factor for hypoxic adaptation, which regulates the transcription of various genes, including inflammation, angiogenesis, and glycolytic metabolism. Recent studies have shown the precise role of HIF in various biological behaviors of BC. More importantly, a new antitumor medication targeting HIF-2 has been used to treat renal cancer. However, therapies targeting HIF-1 in BC have not yet been developed. In this review, we discussed how HIF-1 is expressed and affects the growth, metastasis, and angiogenesis of BC. At the same time, we investigated several HIF-1 inhibitors that provide new perspectives for targeting HIF-1.

Rapid progress is being made in the area of nanotechnology; solid lipid nanoparticles are currently at the forefront of research and development. They have the capability of becoming employed in an extensive number of applications, including the delivery of medications, clinical treatment, and research, in addition to uses in other areas of academic inquiry that could benefit from their utilisation. This article presents a thorough analysis of solid lipid nanoparticles, covering subjects such as their goals, preparation strategy, applications, advantages, and possible remedies for the issues that have been raised. This review provides a discussion of solid lipids that is both in-depth and comprehensive. Studies that investigate the manner in which SLNs are prepared and the routes via which they are administered are typical. Aspects concerning the route of administration of SLNs as well as the destiny of the carriers in vivo are also investigated in this paper.

BACKGROUND: Common primary glomerulonephritis with aberrant mucosal immunity is IgA nephropathy (IgAN). T follicular helper (TFH) cells are essential in regulating B cell differentiation. Peyer's patches (PPs) are the main site where IgA+ plasmablasts differentiate. OBJECTIVE: Our study aimed to investigate the TFH cell's potential contribution to the etiology of IgA nephropathy. MATERIALS AND METHODS: In PPs from IgAN mouse models, the ratio of the TFH cell, B220+IgA+, B220+IgM+, and B220-IgA+ lymphocytes were assessed. Then, we used Western blot to assess the expression of Bcl-6, Blimp- 1, and IL-21 proteins in PPs and used RT-PCR to assess the expression of IL-21 and TGF- 1 mRNA. TFH cells coculture with spleen cells to measure the degree of IL-21 and the ratio of activation marker CD69 on the TFH cells. Naive B cells (CD27-IgD+) from children suffering from IgAN were cultured with TFH cell-related cytokines. The supernatant was detected to assess the excretion of galactose-deficient IgA1 (Gd-IgA1). RESULTS: IgAN mice developed noticeably increased degrees of IL-21 and CD69 on TFH cells than controls did, as well as higher percentages of B220+IgA+, B220+IgM+, B220+IgA+, TGF- 1, and IL-21 mRNA and Bcl-6, IL-21 proteins in PPs. The Gd-IgA1 level in the supernatant and IgAN- positive children's serum were noticeably higher than those of the healthy controls (P < 0.05). PPs provide the microenvironment to induce the production of IgA-secreting plasmablasts. CONCLUSION: TFH cells may be a key moderator to induce B cell differentiation into IgA-secreting plasmablasts and produce Gd-IgA1, which plays a significant part in IgAN's pathogenesis. It could be a new therapeutic target in the future.

BACKGROUND: Long intergenic non-protein coding RNA 1116 (LINC01116) plays a carcinogenic role in a variety of cancers. The study aims to investigate the roles of LINC01116 and hsa-miR-9-5p (miR-9-5p) and fathom their interaction in chordoma. METHOD: The predicted binding sites between miR-9-5p with LINC01116 and phosphoglycerate kinase 1 (PGK1) by starBase were confirmed through dual-luciferase reporter assay. The behaviors of chordoma cells undergoing transfection with siLINC01116 or miR-9-5p inhibitor were determined by Cell Counting Kit-8 (CCK-8), colony formation, Transwell, and flow cytometry assays. The glucose consumption, lactate production, and adenosine triphosphate (ATP) production of chordoma cells were examined with specific kits. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to determine relevant gene expressions in chordoma cells. RESULTS: Silencing of LINC01116 facilitated the apoptosis and expressions of Bcl-2- associated X (Bax), cleaved caspase-3 (C caspase-3) and miR-9-5p while repressing the cell cycle, viability, proliferation, invasion, glucose consumption, lactate production, ATP production, and expressions of PGK1 and Bcl-2. Meanwhile, LINC01116 sponged miR-9-5p, which could target PGK1. Moreover, the miR-9-5p inhibitor acted contrarily and reversed the role of siLINC01116 in chordoma cells. Besides, LINC01116 downregulation facilitated apoptosis and attenuated the proliferation and invasion of chordoma cells as well as PGK1 expression by upregulating miR-9-5p expression. CONCLUSION: LINC01116/miR-9-5p plays a regulatory role in the progression of chordoma cells and is a potential biomarker for chordoma.

Exosomes are vesicles secreted by the plasma membrane of the cells delimited by a lipid bilayer membrane into the extracellular space of the cell. Their release is associated with the disposal mechanism to remove unwanted materials from the cells. Exosomes released from primary tumour sites migrate to other parts of the body to create a metastatic environment for spreading the tumour cells. We have reviewed that exosomes interfere with the tumour progression by (i) promoting angiogenesis, (ii) initiating metastasis, (iii) regulating tumour microenvironment (TME) and inflammation, (iv) modifying energy metabolism, and (v) transferring mutations. We have found that EVs play an important role in inducing tumour drug resistance against anticancer drugs. This review discusses the potential of exosomes to generate a significant therapeutic effect along with improved diagnosis, prognosis, insights on the various research conducted and their significant findings of our interest.

BACKGROUND: Monkeypox is a global public health issue caused by the monkeypox virus (MPXV). As of October 28, 2022, a total of 77,115 laboratory-confirmed cases and 3,610 probable cases, including 36 deaths, were reported, with 9,070 cases reported in Brazil, the second most affected country. The need to develop national technologies for the rapid diagnosis of emerging diseases for mass testing of the population is evident, as observed in the SARS-CoV-2 pandemic. OBJECTIVE: With that in mind, this article provides an overview of current methods, techniques, and their applications in the molecular detection of monkeypox, focusing the search on real-time polymerase chain reaction (qPCR), polymerase chain reaction (PCR), and polymerase chain reaction-enzyme linked immunosorbent assay (PCR-ELISA). METHODS: The relevant documents or papers covered in this study were selected by a search in international bibliographic databases. The search terms used in the databases were aimed at summarizing existing knowledge on molecular diagnostic methods, such as monkeypox; MPX, MPXV, qPCR, PCR, PCR-ELISA, diagnosis and detection searched separately or together using the Boolean operator "AND" either in the title or abstract. The searches took place in September 2022, and the corresponding articles were selected between 2012 and 2022. RESULTS: We found 256 documents in total and twelve studies addressing the molecular diagnosis of monkeypox were classified as possible sources for this review. CONCLUSION: It is evident there is a pressing need to develop national technologies for rapid diagnosis of emerging diseases for mass testing of the population. It is also extremely important to have national detection kits with greater diagnostic capacity to assist in developing effective public policies in countries affected by this disease.

BACKGROUND: The identification in breast cancer (BC) of novel genetic biomarkers regulating natural killer (NK) cell function, including the HLA, KIR, and CD16A (FCGR3A), may be still a challenge. OBJECTIVE: We aimed to evaluate whether the combined effect of these polymorphisms has an impact on BC susceptibility and progression. METHODS: 47 BC Italian patients and healthy individuals (39 females and 66 males/females) were genotyped by Sanger sequencing (HLA-C exon 2-4 and FCGR3A-158V/F, 48L/R/H) and PCR-SSP typing (KIR genes). RESULTS: HLA-C gene allele analysis showed the group C1, with HLA-C*07:02:01 allele, to be significantly associated with tumor progression (16.7% vs. 4.0%, p=0.04, OR=4.867), and instead, group C2, with HLA-C*05:01:01, was protective against disease susceptibility (0.0% vs. 7.2%, p=0.019, OR=0.087). In addition, we highlighted a significant reduction of the KIR2DS4ins in BC patients (pcorr.=0.022) and an increased combined presence of KIR2DL1 and KIR2DS1 genes in advanced BC patients compared to earlier stages (66.7% vs. 19.2%, p=0.002). The concurrent lack of KIR2DL2 and KIR2DS4 genes in the presence of HLA-C2 alleles was significantly associated with increased susceptibility to BC (p=0.012, OR=5.020) or with lymph node involvement (p=0.008, OR=6.375). Lastly, we identified different combinations of the FCGR3A-48/158 variants and KIR genes in BC patients compared to controls. CONCLUSION: Our findings suggest that in the development of BC probably exists a disorder of the NK innate immunity influenced by KIR/HLA-C gene content and FCGR3A-158 polymorphisms and that the combined analysis of these biomarkers might help predict genetic risk scores for tailored screening of BC patients in therapy.

BACKGROUND: It is well recognized that both smoke and Candida infection are crucial risk factors for oral mucosal diseases. The nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and its downstream effectors, interleukin (IL)-1β and IL-18, are pivotal to the host defense against Candida and other pathogens. METHODS: The present study was designed to explore the effects of cigarette smoke and C. albicans on the NLRP3 inflammasome and its downstream signal pathway via in vitro cell model. Oral epithelial cells (Leuk-1 cells) were exposed to cigarette smoke extract (CSE) for 3 days and/or challenged with C. albicans. RESULTS: Microscopically, Leuk-1 cells exerted a defense response to C. albicans by markedly limiting the formation of germ tubes and microcolonies. CSE clearly eliminated the defense response of Leuk-1 cells. Functionally, CSE repressed NLRP3 inflammasome, and IL-1β and IL-18 activation induced by C. albicans in Leuk-1 cells. CONCLUSION: Our results suggested that in oral epithelial cells, the NLRP3 inflammasome might be one of the target pathways by which CSE attenuates innate immunity and leads to oral disorders.

Metabolic syndrome (MetS), which is distinguished by the simultaneous presence of hyperglycemia, dyslipidemia, hypertension, and central obesity, is a critical risk factor for cardiovascular disease (CVDs), mortality, and illness burden. Eliminating about one million cells per second in the human body, apoptosis conserves homeostasis and regulates the life cycle of organisms. In the physiological condition, the apoptotic cells internalize to the phagocytes by a multistep process named efferocytosis. Any impairment in the clearance of these apoptotic cells results in conditions related to chronic inflammation, such as obesity, diabetes, and dyslipidemia. On the other hand, insulin resistance and MetS can disturb the efferocytosis process. Since no study investigated the relationship between efferocytosis and MetS, we decided to explore the different steps of efferocytosis and describe how inefficient dead cell clearance is associated with the progression of MetS.

Sepsis is a fatal organ dysfunction caused by the host's uncontrolled response to infection, with high morbidity and mortality. Early diagnosis and intervention are the most effective methods to reduce the mortality due to sepsis. However, there is still a lack of definite biomarkers or intervention targets for the diagnosis, evaluation, prognosis, and treatment of sepsis. Long non-coding RNAs (lncRNAs) are a type of non-coding transcript with a length ranging from 200 to 100,000 nucleotides. LncRNAs mainly locate in the cytoplasm and nucleus and participate in various signaling pathways related to inflammatory reactions and organ dysfunction. Recent studies have reported that lncRNAs are involved in regulating the pathophysiological process of sepsis. Some classical lncRNAs have been confirmed as promising biomarkers to evaluate the severity and prognosis of sepsis. This review summarizes the mechanical studies on lncRNAs in sepsis-induced acute lung, kidney, myocardial, and liver injuries, analyzes the role of lncRNAs in the pathogenesis of sepsis, and explores the possibility of lncRNAs as potential biomarkers and intervention targets for sepsis-induced multiple organ dysfunction.