Neurodegenerative disorders are among the most common life-threatening disorders among the elderly worldwide and are marked by neuronal death in the brain and spinal cord. Several studies have demonstrated the beneficial role of dietary fatty acids in different brain disorders. This is due to their neurotrophic, antioxidant, and anti-inflammatory properties. Furthermore, extensive evidence shows that an unbalanced intake of certain dietary fatty acids increases the risk of neuropsychiatric diseases. Several research has been done on erucic acid, an ingestible omega-9 fatty acid that is found in Lorenzo's oil. Erucic acid was previously thought to be a natural toxin because of its negative effects on heart muscle function and hepatic steatosis, but it has been discovered that erucic acid is regularly consumed in Asian countries through the consumption of cruciferous vegetables like mustard and rapeseed oil with no evidence of cardiac harm. Erucic acid can also be transformed into nervonic acid, a crucial element of myelin. Therefore, erucic acid may have remyelinating effects, which may be crucial for treating different demyelinating conditions. Also, erucic acid exerts antioxidant and anti-inflammatory effects, suggesting its possible therapeutic role in different neurodegenerative disorders. Considering the fruitful effects of this compound, this article reviews the probable role of erucic acid as a pharmacological agent for treating and managing different neurodegenerative disorders.

mTOR is a serine/threonine kinase that plays various roles in cell growth, proliferation, and metabolism. mTOR signaling in cancer becomes irregular. Therefore, drugs targeting mTOR have been developed. Although mTOR inhibitors rapamycin and rapamycin rapalogs (everolimus, rapamycin, temsirolimus, deforolimus, etc.) and new generation mTOR inhibitors (Rapalink, Dual PI3K/mTOR inhibitors, etc.) are used in cancer treatments, mTOR resistance mechanisms may inhibit the efficacy of these drugs. Therefore, new inhibition approaches are developed. Although these new inhibition approaches have not been widely investigated in cancer treatment, the use of nanoparticles has been evaluated as a new treatment option in a few types of cancer. This review outlines the functions of mTOR in the cancer process, its resistance mechanisms, and the efficiency of mTOR inhibitors in cancer treatment. Furthermore, it discusses the next-generation mTOR inhibitors and inhibition strategies created using nanoparticles. Since mTOR resistance mechanisms prevent the effects of mTOR inhibitors used in cancer treatments, new inhibition strategies should be developed. Inhibition approaches are created using nanoparticles, and one of them offers a promising treatment option with evidence supporting its effectiveness.

Although breast cancer treatment has been developed remarkably in recent years, it remains the primary cause of death among women. Immune checkpoint blockade therapy has significantly altered the way breast cancer is treated, although not all patients benefit from the changes. At present, the most effective mechanism of immune checkpoint blockade application in malignant tumors is not clear and efficacy may be influenced by many factors, including host, tumor, and tumor microenvironment dynamics. Therefore, there is a pressing need for tumor immunomarkers that can be used to screen patients and help determine which of them would benefit from breast cancer immunotherapy. At present, no single tumor marker can predict treatment efficacy with sufficient accuracy. Multiple markers may be combined to more accurately pinpoint patients who will respond favorably to immune checkpoint blockade medication. In this review, we have examined the breast cancer treatments, developments in research on the role of tumor markers in maximizing the clinical efficacy of immune checkpoint inhibitors, prospects for the identification of novel therapeutic targets, and the creation of individualized treatment plans. We also discuss how tumor markers can provide guidance for clinical practice.

Alzheimer's disease (AD) is a specific brain disease that gradually worsens due to dementia over a long period. AD accounts for almost 60% to 80% of cases of dementia. Any damage to neurons affects their ability to communicate, leading to alteration in thinking, behaviour and feelings. Besides mental, motor abilities of an individual may also be affected due to AD. Therefore, it is cardinal to understand the key mechanisms by which either AD progression can be ceased or, after the onset of the disease it could be reverted. Both of these steps need the identification of a particular receptor or a molecular marker through which a drug can enter the neurons. Cholinergic transporters are such potential targets of AD, which regulate the movement of acetylcholine and thus regulate the nerve impulse conduction in the brain. The current article entails information regarding a variety of cholinergic transporters, which will provide a research gap to the global scientific community.

BACKGROUND: schistosomiasis is a neglected tropical parasitic disease caused by trematode worms of the genus schistosoma, which affects approximately 240 million people worldwide. the diagnosis of the disease can be performed by parasitological, molecular, and/or immunological methods, however, the development of new diagnostic methods still essential to guide policy decisions, monitor disease trends and assess the effectiveness of interventions. OBJECTIVE: in this sense, the current work summarizes the findings of a systematic review regarding antigens applied in the enzyme-linked immunosorbent assay test, which were patented and published over the last ten years. METHODS: the literature search strategy used medical subject heading (mesh) terms to define as descriptors. "schistosoma mansoni" was used in arrangement with the descriptors "immunoassay", "enzyme-linked immunosorbent assay", "elisa", and "antigens", using the "and" connector. the patent search was done using keywords, including diagnosis and schistosoma or schistosomiasis or schistosome. several databases were employed for the patent search, such as intellectual property national institute; european patent office; the united states patent and trademark office; patent scope, and google patents. RESULTS: forty-one articles were retrieved, of which only five met the eligibility criteria. seventeen patents were taken from the databases, and a brief description of the most relevant inventions is given here. CONCLUSION: schistosomiasis is considered the most important helminthic disease in worldwide. therefore, it is important to of searching for and develops diagnostic methods based on serology to reduce morbidity and mortality caused by the disease.

As a transcriptional regulation element, the microRNA plays a crucial role in many aspects of molecular biological processes, like cellular metabolism, cell division, cell death, cell movement, intracellular signaling, and immunity. Previous studies suggested that microRNA-214 (miR-214) is probably a valuable cancer marker. In this study, a brief updated overview of the vital dual role of miR-214 in cancer as a tumor suppressor or oncogene was provided. We also examined target genes and signaling pathways related to the dysregulation of miR-214 reported in previous experimental research on various human diseases. To highlight the critical function of miR-214 in the prognostic, diagnostic, and pathogenesis of cancer diseases, we focused on the probable clinical biomarker and drug resistance function of miR-214. The current research provides a comprehensive perspective of the regulatory mechanisms governed by miR-214 in human disease pathogenesis and a list of probable candidates for future study.

INTRODUCTION: MicroRNAs (miRNAs) are a group of small noncoding RNAs (ncRNAs) that post-transcriptionally control the expression of genes by binding and degrading their target mRNAs. miRNAs can function as possible tumor suppressors or oncogenes in various cancers. Lately, miRNAs application as a biomarker (prognosis and diagnosis) for different diseases has gained much attention. miRNAs exist in a stable form in several biological materials, including tissue, plasma, and serum. The noninvasive and easy screening of miRNAs in serum, blood, tissue, and other body fluids and acceptable stability make microRNA a noticeable factor as biomarkers in human malignancies. MATERIALS AND METHODS: In this review, we searched some online databases like Web of Science, Embase, and PubMed to find eligible manuscripts up to the end of 2021. RESULTS: Abnormal expressions of these molecules are associated with the incidence of many illnesses like cancer. Therefore, they are candidates as a molecular tool for noninvasive tumor prognosis and diagnosis. In the current study, we introduce important miRNAs that may be used as prognostic and diagnostic markers in lung cancer patients. CONCLUSION: We summarized the latest reports about critical miRNAs related to the diagnosis and prognosis in lung patients.

Long noncoding RNAs (lncRNAs) are prominent as crucial regulators of tumor establishment and are repeatedly dysregulated in multiple cancers. Therefore, lncRNAs have been identified to play an essential function in carcinogenesis and progression of cancer at genetic and epigenetic levels. FENDRR (fetal-lethal noncoding developmental regulatory RNA) as a LncRNA is a hallmark of various malignancies. FENDRR is crucial for multiple organs' development, such as the lung and heart. The effects of FENDRR under signaling pathways in different cancers have been identified. In addition, it has been verified that FENDRR can affect the development and progression of various cancers. In addition, FENDRR expression has been associated with epigenetic regulation of target genes participating in tumor immunity. Furthermore, FENDRR downregulation was observed in various types of cancers, including colorectal cancer, gastric cancer, pancreatic cancer, cholangiocarcinoma, liver cancer, gallbladder cancer, lung cancer, breast cancer, endometrial cancer, prostate cancer, chronic myeloid leukemia, osteosarcoma, and cutaneous malignant melanoma cells. Here, we review the biological functions and molecular mechanisms of FENDRR in several cancers, and we will discuss its potential as a cancer biomarker and as a probable option for cancer treatment.

MicroRNAs (miRNAs) have been established as key players in various biological processes regulating differentiation, proliferation, inflammation, and autoimmune disorders. Emerging evidence suggests the critical role of miRNAs in the pathogenesis of multiple sclerosis (MS). Here, we provide a comprehensive overview of miRNAs, which are differentially expressed in MS patients or experimental autoimmune encephalomyelitis (EAE) mice and contribute to MS pathogenesis through regulating diverse pathways, including CD4+ T cells proliferation, differentiation, and activation in three subtypes of CD4+ T cells, including Th1, Th17 and regulatory T cells (Tregs). Moreover, the regulation of oligodendrocyte precursor cells (OPC) differentiation as a crucial player in MS pathogenesis is also described. Our literature research showed that miR-223 could affect different pathways involved in MS pathogenesis, such as promoting Th1 differentiation, activating the M2 phenotype of myeloid cells, and clearing myelin debris. MiR-223 was also identified as a potential biomarker, distinguishing relapsing-remitting multiple sclerosis (RRMS) from progressive multiple sclerosis (PMS), and thus, it may serve as an attractive target for further investigations. Our overview provides novel potential therapeutic targets for the treatment and new insights into miRNAs' role in MS pathogenesis.

Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is rarely expressed in normal tissues but highly abundant in pathological diseases, including fibrosis, arthritis, and cancer. Ever since its discovery, we have deciphered its structure and biological properties and continue to investigate its roles in various diseases while attempting to utilize it for targeted therapy. To date, no significant breakthroughs have been made in terms of efficacy. However, in recent years, several practical applications in the realm of imaging diagnosis have been discovered. Given its unique expression in a diverse array of pathological tissues, the fundamental biological characteristics of FAP render it a crucial target for disease diagnosis and immunotherapy. To obtain a more comprehensive understanding of the research progress of FAP, its biological characteristics, involvement in diseases, and recent targeted application research have been reviewed. Moreover, we explored its development trend in the direction of clinical diagnoses and treatment.

Puberty is initiated from the continuous and growing pulsatile secretion of gonadotropin-releasing hormone (GnRH) in the hypothalamus and then the activation of the hypothalamic-pituitary-gonadal (HPG) axis. Numerous factors involve pubertal initiation, whose abnormality may come from the dysfunction of these regulators. Makorin RING finger protein 3 (MKRN3) inhibits the secretion of GnRH and plays indispensable roles during the development of pubertal onset, and mutations of MKRN3 showed the commonest genetic cause of central precocious puberty (CPP). Recently, growing studies have revealed the functional mechanisms of MKRN3 in the pubertal initiation and the occurrence of CPP. In this review, we mainly summarized the research advances on the roles of MKRN3 in the development of pubertal onset and their underpinning mechanisms, contributing to a better understanding of the precise mechanisms of pubertal initiation and the pathogenesis of CPP.

INTRODUCTION: HERVs are human endogenous retroviruses, which represent about 8% of the human genome, and have various physiological functions, especially in pregnancy, embryo development and placenta formation. However, their involvement in diseases is not well defined. Some studies have observed changes in HERV expression according to age. OBJECTIVE: Therefore, the aim of this systematic review was to analyze their role in pathogenesis and usage as diagnosis or prognosis biomarkers in aging disorders. METHODS: In this study, a search on the Pubmed interface was performed for papers published from January 1953 to June 1st, 2021. RESULTS: 45 articles have been included, which matched the eligibility criteria and evaluated the following diseases: breast cancer, prostate cancer, amyotrophic lateral sclerosis (ALS), osteoarthritis, Alzheimer's disease, immuno-senescence, cognitive impairment, cataract, glaucoma and hypertension. CONCLUSION: In conclusion, the results suggested that HERVs play a role in the pathogenesis and can be used as biomarkers for the diagnosis or prognosis of aging disorders.

BACKGROUND: Psoralidin (PL) could affect the differentiation of bone marrow mesenchymal stem cells (BMSCs). The role of PL is still unclear in adipose-derived stem cells (ADSCs). AIMS: This study aimed to investigate the effects of PL on ADSCs differentiation into nucleus pulposus-like cells and the TGF-β/Smad signaling pathway. METHODS: The proliferation and apoptosis of ADSCs were detected. The nucleus pulposus cell-related markers (CD24, BASP1, KRT19, and Aggrecan) and TGF-β/Smad signaling pathway indexes were analyzed. RESULTS: The results showed that compared to the control group, the cell activity was increased in the PL group, and the apoptosis rate was decreased. The mRNA and protein levels of nucleus pulposus cells markers (CD24, BASP1, KRT19, Aggrecan, and Collagen Type II) and TGF-β/Smad signaling pathway-related indexes (TGF-β, SMAD2, and SMAD3) were increased in PL group. After treatment with PL and TGF-β silencing, the TGF-β/Smad signaling pathway-related indicators (TGF-β, SMAD2, and SMAD3) and nucleus pulposus cells markers (CD24, BASP1, KRT19, Aggrecan, and Collagen Type II) were found to be higher in the sh-TGF-β +PL group than in the sh-TGF-β group. CONCLUSION: In conclusion, our study showed that PL might induce the differentiation of ADSCs to nucleus pulposus cells through the TGF-β/Smad signaling pathway. It might have the potential application value in the treatment of intervertebral disc degeneration.

BACKGROUND: Angiogenesis of tumor cells is highly associated with tumorsecreted factors and matrix proteins. However, the underlying mechanism of tumorsecreted factors and matrix proteins during angiogenesis is rarely discussed. OBJECTIVES: This study investigated the relationship between the maternally expressed gene 3 (MEG3), a tumor-secreted growth factor, and Decorin, a tumor-secreted matrix protein, and evaluated their derivate roles in human endothelial cell development. METHODS: Human endothelial cells were transiently transfected with a plasmid expressing antisense of Decorin mRNA (shDecorin) and silencing mRNA of MEG3 (siMEG3) or MEG3 over-expressive vectors. A series of qPCR and Western blot analysis was applied to characterize the expressions of MEG3 and Decorin in all transfected cells. Moreover, scratch, Transwell, and Matrigel neovascularization assays were performed to examine three key processes of endothelial cells' angiogenesis, including tubulogenesis, proliferation, and migratory levels. In addition, the cell viability was evaluated at each step via the MTT test. RESULTS: The overexpression of MEG3 inhibited angiogenesis and migration of endothelial cells by preventing the expression of Decorin. At the same time, the inhibition of MEG3 via siRNA resulted in an increased expression of Decorin, enhanced tube formation levels, and promoted endothelial cell proliferation and migration. Furthermore, Decorin's knockdown suppressed the angiogenesis and migration of endothelial cells without affecting the expression of MEG3. Importantly, the stimulation of HUVEC cells with exogenous Decorin protein alleviated most phenotypes induced by the upregulation of MEG3. CONCLUSION: Our study demonstrated the anti-growth effects of MEG3 on vasculogenesis and migration of endothelial cells. Thus, by blocking the expression of Decorin in HUVECs, the overexpression of MEG3 repressed their development and might potentially alleviate the ischemic stroke.

BACKGROUND: The c-ETS-1 (ETS1) expression is high in clear cell renal cell carcinoma (ccRCC) tissues; however, how it impacts ccRCC is currently unknown. METHOD: The online STRING web source was used to construct a protein network interacting with ETS1. The Cell Counting Kit-8 was used to detect the cell viability. A clonogenic assay, a wound-healing assay, and a Transwell assay were used to detect cell proliferation, invasion and migration abilities. Western blot was used to detect the expression of proteins. RESULT: The data showed the expression of ETS1 in ccRCC tissues to be significantly increased compared to adjacent tissues (p<0.05). The positive expression of ETS1 in ccRCC patients aged 20-100 was statistically significant compared to adjacent normal tissues (p<0.05). The grade of ETS1 positive expression (1-4) and lymph node metastasis (N1) in ccRCC were significantly higher than those in adjacent normal tissues (p<0.05). The tumour stage (stages 1-4) in ccRCC patients with positive ETS1 expression was significantly higher than that in adjacent normal tissues (p<0.05). Knockdown of ETS1 and PERK inhibitors significantly inhibited the proliferation, migration and invasion of ccRCC cells. Knockdown of ETS1 inhibited MMP-2 expression, and an extracellular signal-related kinase (ERK) inhibitor inhibited both ETS1 and MMP-2 expression. CONCLUSION: A high expression of ETS1 is associated with the progression of ccRCC. This study suggests that ETS1 promotes proliferation by increasing MMP2 expression in ccRCC, and combined knockdown of ETS1 and inhibition of ERK can significantly inhibit the proliferation, migration and invasion of ccRCC. ETS1 may be a therapeutic and prognostic target for renal cell carcinoma.

BACKGROUND: Radiofrequency ablation (RFA) is an important treatment strategy for patients with advanced hepatocellular carcinoma (HCC). However, its therapeutic effect is unsatisfactory and recurrence often occurs after RFA treatment. The octamer-binding transcription factor OCT1 is a novel tumour-promoting factor and an ideal target for HCC therapy. OBJECTIVE: This study aimed to expand the understanding of HCC regulation by OCT1. METHODS: The expression levels of the target genes were examined using qPCR. The inhibitory effects of a novel inhibitor of OCT1 (NIO-1) on HCC cells and OCT1 activation were examined using Chromatin immunoprecipitation or cell survival assays. RFA was performed in a subcutaneous tumour model of nude mice. RESULTS: Patients with high OCT1 expression in the tumour tissue had a poor prognosis after RFA treatment (n = 81). The NIO-1 showed antitumor activity against HCC cells and downregulated the expression of the downstream genes of OCT1 in HCC cells, including those associated with cell proliferation (matrix metalloproteinase-3) and epithelial-mesenchymal transition-related factors (Snail, Twist, N-cadherin, and vimentin). In a subcutaneous murine model of HCC, NIO-1 enhanced the effect of RFA treatment on HCC tissues (n = 8 for NIO-1 and n=10 for NIO-1 + RFA). CONCLUSION: This study demonstrated the clinical importance of OCT1 expression in HCC for the first time. Our findings also revealed that NIO-1 aids RFA therapy by targeting OCT1.

RESEARCH BACKGROUND: Breast cancer is the second leading cause of death all over the world and is not only limited to females but also affects males. For estrogen receptor-positive breast cancer, tamoxifen has been considered the gold-line therapy for many decades. However, due to the side effects associated with the use of tamoxifen, its use is only limited to individuals in high-risk groups and limits its clinical application to moderate and/or lower-risk groups. Thus, there is a necessity to decrease the dose of tamoxifen, which can be achieved by targeting the drug to breast cancer cells and limiting its absorption to other body parts. PROBLEM STATEMENT: Artificial antioxidants used in the formulation preparation are assumed to upsurge the risk of cancer and liver damage in humans. The need of the hour is to explore bio-efficient antioxidants from natural plant sources as they are safer and additionally possess antiviral, anti-inflammatory, and anticancer properties. Objectives of the study and research: The objective of this hypothesis is to prepare tamoxifen-loaded PEGylated NiO nanoparticles using green chemistry, tumbling the toxic effects of the conventional method of synthesis for targeted delivery to breast cancer cells. Significance of the research work: The significance of the work is to hypothesize a green method for the synthesis of NiO nanoparticles that are eco-friendly, cost-effective, decrease multidrug resistance, and can be used for targeted therapy. Garlic extract contains an organosulfur compound (Allicin) which has drug-metabolizing, anti-oxidant, and tumour growth inhibition effects. In breast cancer, allicin sensitizes estrogen receptors, increasing the anticancer efficacy of tamoxifen and reducing offsite toxicity. Thus, this garlic extract would act as a reducing agent and a capping agent. The use of nickel salt can help in targeted delivery to breast cancer cells and, in turn, reduces drug toxicity in different organs. Future directions/recommendations: This novel strategy may aim for cancer management with less toxic agents acting as an apt therapeutic modality.

Colorectal cancer (CRC) is one of the world's most common types of malignancy. The proliferation of precancerous lesions causes this type of cancer. Two distinct pathways for CRC carcinogenesis have been identified: the conventional adenoma-carcinoma pathway and the serrated neoplasia pathway. Recently, evidence has demonstrated the regulatory roles of noncoding RNAs (ncRNAs) in the initiation and progression of precancerous lesions, especially in the adenoma-carcinoma pathway and serrated neoplasia pathway. By expanding the science of molecular genetics and bioinformatics, several studies have identified dysregulated ncRNAs that function as oncogenes or tumor suppressors in cancer initiation and formation by diverse mechanisms via intracellular signaling pathways known to act on tumor cells. However, many of their roles are still unclear. This review summarizes the functions and mechanisms of ncRNAs (such as long non-coding RNAs, microRNAs, long intergenic non-coding RNAs, small interfering RNAs, and circRNAs) in the initiation and formation of precancerous lesions.

Attention-deficit hyperactivity disorder (ADHD) is a neurobiological and neurodevelopmental disorder with an idiosyncratic genetic base. ADHD presents various characteristics, such as inattention, hyperactivity, and impulsivity. Over the period, ADHD leads to noticeable functional disability. A five- to ten-fold progressed risk of disorder development is observed in the populations with familial history of ADHD. The abnormal structure of the brain in ADHD results in altered neural mechanisms, such as cognition, attention, and memorial function. The mesolimbic, nigrostriatal, and mesocortical pathways in the brain get affected by the deterioration of the levels of dopamine. The hypothesis of dopamine in ADHD and its etiopathology suggests that detained attention and impaired arousal functions are due to reduced levels of dopamine. The quickest way to improve strategical treatment is by clarifying the etiological aspects of ADHD and identifying the underlying mechanisms of pathophysiology, which will assist in exploring the biomarkers for better diagnosis. The implementation of life course theory is a very important research principle announced by Grand Challenges in Global Health Initiative (GCMHI). Long-term research is needed to define the progression of ADHD. Interdisciplinary collaborations promise a great future for research innovations in ADHD.

BACKGROUND: Alpinetin, a natural flavonoid, has been shown to have anticancer effects on many tumors. This study investigated the antitumor effect of alpinetin on renal clear cell carcinoma (ccRCC). METHODS: Network Pharmacology analysis was carried out on the targets and molecular mechanisms of alpinetin treating ccRCC. The Annexin V PE/7-AAD kit was used to detect apoptosis. Flow cytometry and Cell Counting Kit-8 (CCK-8) were used to detect cell proliferation and cycle. A 24-well transwell chamber and the ibidi scratch insertion performed cell migration analysis. The protein expression of the target molecule was detected by Western blotting. Nude mouse tumorigenesis assays were used to determine the in vivo antitumor effects of alpinetin. RESULTS: The network pharmacology revealed that GAPDH, HRAS, SRC, EGFR, and AKT1 are the main targets of alpinetin in treating ccRCC, with the PI3K/AKT signaling pathway being the main pathway of action. We found that alpinetin could significantly inhibit the proliferation and migration of ccRCC cells by inducing apoptosis. In addition, alpinetin also inhibited the cycle progression of ccRCC cells by blocking them in the G1 phase. Furthermore, in vivo and in vitro, alpinetin could inhibit the activation of an important pathway involved in the proliferation and migration of ccRCC cells, namely the PI3K/Akt pathway. CONCLUSION: Alpinetin can inhibit the growth of ccRCC cells by inhibiting the activation of the PI3K/Akt pathway and can be a potential anti-cancer drug for ccRCC.

Natural remedies from a range of sources, including plants, animals, microorganisms, and marine life, have made a significant contribution to the treatment of many ailments. Lavender is a Mediterranean shrub from the Lamiaceae family. Lavender flowers (Lavandula flores) include active ingredients (3%), anthocyanins, sugars, phytosterols, minerals, and tannins and are majorly used for herbal applications. Lavender essential oil's descriptive and analytical composition varies depending on genotype, growing region, climatic circumstances, propagation, and morphological characteristics. There are around 300 chemical components in essential oil. Linalool, terpinen-4-ol, linalyl acetate, ocimene, acetate lavandulol, and cineole are the most prominent constituents. Lavender oil has antibacterial and antioxidant properties. The lavender extract helps to prevent dementia and may slow cancer cell growth, while lavender oil is used to treat skin problems. This review will cover the recent medical, economic and regional advancements in levander propagation and how the Council of Scientific & Industrial Research Indian Institute of Integrative (CSIR IIIM) aroma mission is actively acting as a bridge between farmers and their economic improvement by attracting them to the field of medicinal plant cultivation.

BACKGROUND: Calcium dobesilate (CaD) is a microvascular protective agent that can significantly improve kidney function by reducing urinary protein, serum creatinine, and urea nitrogen levels. The effects of CaD on ischemia-reperfusion-induced acute kidney injury (AKI) were investigated in this study. METHOD: In this study, The Balb/c mice were randomly divided into (1) sham group, (2) I/R group, (3) I/R group + CaD (50 mg/kg) and (4) I/R group + CaD (500 mg/kg). After treatment, serum creatinine and urea nitrogen were detected. The levels of superoxide dismutase (SOD) and malonaldehyde (MDA) were examined. Then, the effects of CaD H2O2-damaged HK-2 cells were investigated, as reflected by the results of cell viability, reactive oxygen species (ROS) level, apoptosis and markers of kidney injury. RESULTS: The results showed that CaD treatment effectively attenuated the renal functions, pathological changes, and oxidative stress in I/R-induced AKI mice. It effectively reduced ROS production and improved MMP and apoptosis in H2O2-damaged HK-2 cells. The increased expression of apoptosis-related proteins and kidney injury biomarkers were significantly ameliorated after CaD treatment. CONCLUSION: Overall, CaD effectively ameliorated renal injury by eliminating ROS and demonstrated in vivo and in vitro for I/R-induced AKI. CaD has been shown to be a promising therapeutic agent for the treatment of I/R-induced AKI.

BACKGROUNDS: Glaucoma is the second leading cause of blindness. Apoptosis of retinal ganglion cells (RGCs) is an important mechanism of glaucomatous optic injury. Rho kinase expression is significantly increased in apoptotic RGCs. This study aimed to investigate the role of RhoA, a Rho GTPase, on the survival of RGCs and further to explore its potential therapeutic applications. METHODS: RGCs were treated with siRhoA for 24 hours in vitro. Knockdown of RhoA was confirmed with quantitative RT-PCR. Oxidative stress was induced by treating the RGCs with 200 μM of H2O2 for 1 hour, and apoptosis of RGCs was quantified with TUNEL assay in situ, and with flow cytometry. The mRNA expression levels of RhoA, Nogo receptor, caspase 3 and Bcl-2 were evaluated by quantitative RT-PCR, and the protein levels of RhoA, ROCK1, ROCK2, Nogo receptor, caspase 3 and Bcl-2 were evaluated by Western blot. We found siRhoA treatment efficiently downregulated the expression of RhoA in RGCs and protected against H2O2-induced injury in RGCs in vitro. Apoptosis of RGC cells under oxidative stress was quantified in situ using TUNEL assay and confirmed with flow cytometry (FCM). RESULTS: With the knockdown of RhoA, the expression of ROCK1, ROCK2, Nogo Receptor, Casepase-3 were decreased, while the expression of Bcl-2 was increased in both mRNA and protein level. Our data indicated that siRhoA prevented H2O2-induced apoptosis in RGC cells by modulating the RhoA/ROCK pathway. CONCLUSION: The results suggested that siRhoA may exert potentially effective neuroprotection for RGCs by reducing injury.

In recent years, there has been a significant increase in the practice of regenerative medicine by health practitioners and direct-to-consumer businesses globally. Among different tools of regenerative medicine, platelet-rich plasma (PRP) and stem cell-based therapies have received considerable attention. The use of PRP, in particular, has gained popularity due to its easy access, simple processing techniques, and regenerative potential. However, it is important to address a common misconception amongst the general public equating to PRP and stem cells due to the demonstrated efficacy of PRP in treating musculoskeletal and dermatological disorders. Notably, PRP promotes regeneration by providing growth factors or other paracrine factors only. Therefore, it cannot replenish or replace the lost cells in conditions where a large number of cells are required to regenerate tissues and/or organs. In such cases, cell-based therapies are the preferred option. Additionally, other tools of regenerative medicine, such as bioprinting, organoids, and mechanobiology also rely on stem cells for their success. Hence, healthcare and commercial entities offering direct-to-customer regenerative therapies should not mislead the public by claiming that the application of PRP is a stem cell-based therapy. Furthermore, it is important for regulatory bodies to strictly monitor these profit-driven entities to prevent them from providing unregulated regenerative treatments and services that claim a broad variety of benefits with little proof of efficacy, safety concerns, and obscure scientific justification.

Natural killer (NK) cells are among the most important cells in innate immune defense. In contrast to T cells, the effector function of NK cells does not require prior stimulation and is not MHC restricted. Therefore, chimeric antigen receptor (CAR)-NK cells are superior to CAR-T cells. The complexity of the tumor microenvironment (TME) makes it necessary to explore various pathways involved in NK cell negative regulation. CAR-NK cell effector function can be improved by inhibiting the negative regulatory mechanisms. In this respect, the E3 ubiquitin ligase tripartite motif containing 29 (TRIM29) is known to be involved in reducing NK cell cytotoxicity and cytokine production. Also, targeting TRIM29 may enhance the antitumor efficacy of CAR-NK cells. The present study discusses the negative effects of TRIM29 on NK cell activity and genomic deletion or suppression of the expression of TRIM29 as a novel approach to optimize CAR-NK cell-based immunotherapy.

BACKGROUND: Extensive deposition of extracellular matrix (ECM) in idiopathic pulmonary fibrosis (IPF) is due to hyperactivation and proliferation of pulmonary fibroblasts. However, the exact mechanism is not clear. OBJECTIVE: This study focused on the role of CTBP1 in lung fibroblast function, elaborated its regulation mechanism, and analyzed the relationship between CTBP1 and ZEB1. Meanwhile, the anti-pulmonary fibrosis effect and its molecular mechanism of Toosendanin were studied. METHODS: Human IPF fibroblast cell lines (LL-97A and LL-29) and normal fibroblast cell lines (LL-24) were cultured in vitro. The cells were stimulated with FCS, PDGF-BB, IGF-1, and TGF-β1, respectively. BrdU detected cell proliferation. The mRNA expression of CTBP1 and ZEB1 was detected by QRT-PCR. Western blotting was used to detect the expression of COL1A1, COL3A1, LN, FN, and α-SMA proteins. An animal model of pulmonary fibrosis was established to analyze the effects of CTBP1 silencing on pulmonary fibrosis and lung function in mice. RESULTS: CTBP1 was up-regulated in IPF lung fibroblasts. Silencing CTBP1 inhibits growth factor-driven proliferation and activation of lung fibroblasts. Overexpression of CTBP1 promotes growth factor-driven proliferation and activation of lung fibroblasts. Silencing CTBP1 reduced the degree of pulmonary fibrosis in mice with pulmonary fibrosis. Western blot, CO-IP, and BrdU assays confirmed that CTBP1 interacts with ZEB1 and promotes the activation of lung fibroblasts. Toosendanin can inhibit the ZEB1/CTBP1protein interaction and further inhibit the progression of pulmonary fibrosis. CONCLUSION: CTBP1 can promote the activation and proliferation of lung fibroblasts through ZEB1. CTBP1 promotes lung fibroblast activation through ZEB1, thereby increasing excessive deposition of ECM and aggravating IPF. Toosendanin may be a potential treatment for pulmonary fibrosis. The results of this study provide a new basis for clarifying the molecular mechanism of pulmonary fibrosis and developing new therapeutic targets.