Current Molecular Medicine - Volume 24, Issue 1, 2024

At present, timely and accurate diagnosis and effective treatment of Epstein- Barr Virus (EBV) infection-associated fever remain a difficult challenge. EBV encodes 44 mature microRNAs (miRNAs) that inhibit viral lysis, adjust inflammatory response, regulate cellular apoptosis, promote tumor genesis and metastasis, and regulate tumor cell metabolism. Herein, we have collected the specific expression data of EBV-miRNAs in EBV-related fevers, including infectious mononucleosis (IM), EBVassociated hemophagocytic lymphohistiocytosis (EBV-HLH), chronic active EBV infection (CAEBV), and EBV-related tumors, and proposed the potential value of EBVmiRNAs as biomarkers to assist in the identification, diagnosis, and prognosis of EBVrelated fever, as well as therapeutic targets for drug development.

SARS-CoV2 is a novel respiratory coronavirus and, understanding its molecular mechanism is a prerequisite to developing effective treatment for COVID-19. This RNA genome-carrying virus has a protein coat with spikes (S) that attaches to the ACE2 receptor at the cell surface of human cells. Several repurposed drugs are used to treat COVID-19 patients that are proven to be largely unsuccessful or have limited success in reducing mortalities. Several vaccines are in use to reduce the viral load to prevent developing symptoms. Major challenges to their efficacy include the inability of antibody molecules to enter cells but remain effective in the bloodstream to kill the virus. The efficacy of vaccines also depends on their neutralizing ability to constantly evolve new virus strains due to novel mutations and evolutionary survival dynamics. Taken together, SARS-CoV2 antibody vaccines may not be very effective and other approaches based on genetic, genomic, and protein interactome could be fruitful to identify therapeutic targets to reduce disease-related mortalities.

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.

Genistein is a flavonoid, mostly found in soybean extract and is widely used for its antioxidant and anti-inflammatory activities. Genistein can interact with estrogen receptors due to its structural similarities to estrogen. It also inhibits protein tyrosine kinases and affects a variety of intracellular signal transductions. Genistein attenuates oxidative stress via diverse cellular mechanisms. However, nuclear factor (erythroidderived 2)-like 2 (Nrf2), the main antioxidant regulator, potentiates genistein's antioxidant effects and reduces cell damage. Nrf2 includes of seven domains and controls the expression of the phase II antioxidant enzymes to decrease oxidative stress. In this review, we address findings related to Nrf2 signaling pathways in the context of genistein's effects on diverse human diseases.

An increasing volume of studies has reported that long non-codingRNAs (lncRNAs) are involved in the carcinogenesis of many different cancers. Especially in gastrointestinal tumors, lncRNAs are found to participate in various physiological and pathological processes. LncRNAs can regulate gene expression at multiple levels, including transcriptional, post-transcription, translational, and post-translational levels. Long intergenic non-protein coding RNA 665(LINC00665), a novel cancer-related lncRNA, is frequently dysregulated in multiple gastrointestinal tumors, including gastric and colorectal cancers, hepatocellular carcinoma, and so on. In this review, we analyzed the expression and prognostic value of LINC00665 in human gastrointestinal tumors, systematically summarized the current literature about the clinical significance of this lncRNA, and explored the regulatory mechanisms of LINC00665 as a competing endogenous RNA (ceRNA) in tumor progression. Consequently, we concluded that LINC00665 might act as a prognostic biomarker and a potential target for gastrointestinal tumor diagnosis and treatment.

Stroke causes brain damage and is one of the main reasons for death. Most survivors of stroke face long-term physical disabilities and cognitive dysfunctions. In addition, they also have persistent emotional and behavioral changes. The two main treatments that are effective are reperfusion with recombinant tissue plasminogen activator and recanalization of penumbra using mechanical thrombectomy. However, these treatments are suitable only for a few patients due to limitations such as susceptibility to hemorrhage and the requirement for administering tissue plasminogen activators within the short therapeutic window during the early hours following a stroke. The paucity of interventions and treatments could be because of the multiple pathological mechanisms induced in the brain by stroke. The ongoing immune response following stroke has been attributed to the worsening brain injury. Hence, novel compounds with immunomodulatory properties that could improve the outcome of stroke patients are required. Natural compounds and medicinal herbs with anti-inflammatory activities and having minimal or no adverse systemic effect could be beneficial in treating stroke. Ocimum sanctum is a medicinal herb that can be considered an effective therapeutic option for ischemic brain injury. Ocimum sanctum, commonly known as holy basil or "Tulsi," is mentioned as the "Elixir of Life" for its healing powers. Since antiquity, Tulsi has been used in the Ayurvedic and Siddha medical systems to treat several diseases. It possesses immuno-modulatory activity, which can alter cellular and humoral immune responses. Tulsi can be considered a potential option as an immuno-modulator for treating various diseases, including brain stroke.In this review, we will focus on the immunomodulatory properties of Tulsi, specifically its effect on both innate and adaptive immunity, as well as its antioxidant and antiinflammatory properties, which could potentially be effective in treating ongoing immune reactions following ischemic brain injury.

Secondary metabolites are an important part to play a major role in society and it was isolated from plant flavonoids and useful in the treatment of various kinds of diseases in the human race. They are widely used as food and nutrition supplements as well as antioxidants. Traditionally, the Desmodium species are an important tool for the secondary metabolites to treat various diseases. Desmodium triquetrum (Fabaceae) one of the Indian medicinal plants is widely used in the treatment of asthma and inflammation. Three flavonoids isolated from Desmodium triquetrum Linn namely Baicalein, Naringin and Neohesperidin are useful as antioxidants, food and nutrition supplements, that help the body to function efficiently while protecting it against toxins as well stressors. The role of flavonoids may be due to the presence of the phenolic compound. Similarly, the flavonoids such as gangetin, gangetinin, desmocarpin and desmodin isolated from the species Desmodium gangeticum are responsible for antileishmanial, antioxidant, anti-arthritic, and immunomodulatory activities. Additionally, isolated flavanoids from the species Desmodium triflorum show antibacterial, antiepileptic, antifungal, and radioprotective activities. So, the aim of the present study, based on the literature miming from the desmodium species is to acknowledge the importance of flavonoids in human health as dietary food supplements and therapeutic uses.

Urothelial carcinoma (UC) is a common malignancy that remains a clinical challenge: Non-muscle-invasive urothelial carcinoma (NMIUC) has a high rate of recurrence and risk of progression, while muscle-invasive urothelial carcinoma (MIUC) has a high mortality. Although some new treatments, such as immunotherapies, have shown potential effects on some patients, most cases of advanced UC remain incurable. While treatments based on epigenetic mechanisms, whether combined with traditional platinum-based chemotherapy or emerging immunotherapy, show therapeutic advantages. With the advancement of sequencing and bioinformatics, the study of epigenomics, containing DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA, is increasingly linked with the occurrence and progression of UC. Since the epigenetics of UC is a constantly developing field of medicine, this review aims to summarize the latest research on epigenetic regulation of UC, generalize the mechanism of epigenetics in UC, and reveal the potential epigenetic therapies in the clinical setting, in order to provide some new clues on the discovery of new drugs based on the epigenetics.

The idea of cancer immunotherapy has spread, and it has made tremendous progress with the advancement of new technology. Immunotherapy, which serves to assist the natural defenses of the body in eradicating cancerous cells, is a remarkable achievement that has revolutionized both cancer research and cancer treatments. Currently, the use of stem cells in immunotherapy is widespread and shares a special characteristic, including cancer cell migration, bioactive component release, and immunosuppressive activity. In the context of cancer, mesenchymal stem cells (MSCs) are rapidly being identified as vital stromal regulators of tumor progression. MSCs therapy has been implicated in treating a wide range of diseases, including bone damage, autoimmune diseases, and particularly hematopoietic abnormalities, providing stem cell-based therapy with an extra dimension. Moreover, the implication of MSCs does not have ethical concerns, and the complications known in pluripotent and totipotent stem cells are less common in MSCs. MSCs have a lot of distinctive characteristics that, when coupled, make them excellent for cellular-based immunotherapy and as vehicles for gene and drug delivery in a variety of inflammations and malignancies. MSCs can migrate to the inflammatory site and exert immunomodulatory responses via cell-to-cell contacts with lymphocytes by generating soluble substances. In the current review, we discuss the most recent research on the immunological characteristics of MSCs, their use as immunomodulatory carriers, techniques for approving MSCs to adjust their immunological contour, and their usages as vehicles for delivering therapeutic as well as drugs and genes engineered to destroy tumor cells.

Introduction: Lung cancer is common cancer with high mortality. A growing number of studies have focused on investigating the regulatory effects of microRNAs (miRs/miRNAs) during cancer progression. Nevertheless, the biological function of miR- 34c-5p in lung cancer and the underlying mechanism have not been determined. This study explored the effect of miR-34c-5p on the malignant behaviors of lung cancer cells.Methods: In this study, we utilized diverse public databases to obtain differentially expressed miRNAs. Then, qRT-PCR and western blot were conducted to determine miR-34c-5p and transducin β-like 1 X-linked receptor 1 (TBL1XR1) expression. Next, H1299 and H460 cells were transfected with miR-34c-5p-mimic and pcDNA3.1- TBL1XR1. To examine the anticancer effects of miR-34c-5p, CCK-8, scratch, and Matrigel-Transwell assays were conducted to test cell viability, migration, and invasion, respectively. The StarBase database and dual-luciferase reporter gene assay were used to predict and verify the relationship between miR-34c-5p and TBL1XR1.Results: Finally, Wnt/β-catenin signaling- and epithelial-mesenchymal transition (EMT)- related protein levels were detected using western blot. The results demonstrated that miR-34c-5p was poorly expressed in lung cancer cells, while TBL1XR1 was highly expressed. The findings also confirmed the direct interaction between miR-34c-5p and TBL1XR1. In H1299 and H460 cells, miR-34c-5p overexpression inhibited cell proliferation, migration, and invasion, Wnt/β-catenin signaling activity, and EMT, while TBL1XR1 upregulation reversed these effects of miR-34c-5p overexpression.Conclusion: These findings illustrated that miR-34c-5p might repress the malignant behaviors of lung cancer cells via TBL1XR1, providing evidence for miR-34c-5p-based lung cancer therapy.

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 antipulmonary 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.

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.

Aim: We present a Direct SARS-CoV-2 Detection System that achieves sample-to-results in less than two hours in three simple steps.Methods: The Detection System includes Direct one-step Reverse Transcription PCR (RT-PCR) reagents (Qexp-MDx kit), a portable thermal cycler (Qampmini) with a preprogrammed chip and a simple-to-use Capillary Gel Electrophoresis system (Qsep Series Bio-Fragment Analyzer) with high fluorescence detection sensitivity to solve the problems associated with traditional real-time PCR (qPCR) systems which produces high false positive results.Results: The proposed simple-to-use detection platform can provide high detection sensitivity (identify less than 20 copies) and fast results (less than 120 minutes), which would be suitable for field testing applications.Conclusion: Our high detection sensitivity platform provides fast and accurate results in 120 minutes without doing DNA/RNA extraction.