Current Molecular Medicine - Volume 24, Issue 6, 2024

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, cellbased 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 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.

The ubiquitous pandemic that emerged due to COVID-19 affected the whole planet. People all over the globe became vulnerable to the unpredictable emergence of coronavirus. The sudden emergence of respiratory disease in coronavirus infected several patients. This affected human life drastically, from mild symptoms to severe illness, leading to mortality. COVID-19 is an exceptionally communicable disease caused by SARS-CoV-2. According to a genomic study, the viral spike RBD interactions with the host ACE2 protein from several coronavirus strains and the interaction between RBD and ACE2 highlighted the potential change in affinity from the virus causing the COVID-19 outbreak to a progenitor type of SARS-CoV-2. SARS-CoV-2, which could be the principal reservoir, is phylogenetically related to the SARS-like bat virus. Other research works reported that intermediary hosts for the transmission of viruses to humans could include cats, bats, snakes, pigs, ferrets, orangutans, and monkeys. Even with the arrival of vaccines and individuals getting vaccinated and treated with FDAapproved repurposed drugs like Remdesivir, the first and foremost steps aimed towards the possible control and minimization of community transmission of the virus include social distancing, self-realization, and self-health care. In this review paper, we discussed and summarized various approaches and methodologies adopted and proposed by researchers all over the globe to help with the management of this zoonotic outbreak by following repurposed approaches.

Background: For any drug molecule, it is mandatory to pass the drug approval process of the concerned regulatory authority, before being marketed. The Food and Drug Administration (FDA), throughout the year, approves several new drugs for safety and efficacy. In addition to new drug approvals, FDA also works on improving access to generic drugs, aimed to lower the cost of drugs for patients and improve access to treatments. In the year 2022 twelve new drug therapies were approved for managing varying cancers. Methods: This manuscript is focused to describe the pharmacological aspects including therapeutic uses, mechanisms of actions, pharmacokinetics, adverse effects, doses, indication for special cases, contraindications, etc., of novel FDA-approved anticancer drug therapies in the year 2022. Result: FDA has approved about 29% (11 out of 37) novel drug therapies for varying types of cancers such as lung cancer, breast cancer, prostate cancer, melanoma, leukemia, etc. The Center for Drug Evaluation and Research CDER has reported that 90% of these anticancer drugs (e.g. Adagrasib, Futibatinib, Mirvetuximabsoravtansinegynx, Mosunetuzumab-axb, Nivolumab and relatlimab-rmbw, Olutasidenib, Pacritinib, Tebentafusp-tebn, Teclistamab-cqyv, and Tremelimumab-actl) as orphan drugs and recommended to treat rare or uncommon cancers such as non-small cell lung cancer, metastatic intrahepatic cholangio-carcinoma, epithelial ovarian cancer, follicular lymphoma, metastatic melanoma, metastatic uveal melanoma, etc. CDER has identified six anticancer drugs (e.g. Lutetium (¹⁷⁷;Lu)vipivotidetetraxetan, Mirvetuximabsoravtansine- gynx, Mosunetuzumab-axb, Nivolumab and relatlimab-rmbw, Tebentafusp-tebn, Teclistamab-cqyv) as first-in-class drugs i.e. drugs having different mechanisms of action from the already existing ones. The newly approved anticancer drugs shall provide more efficient treatment options for cancer patients. Three FDA-approved anticancer drugs in the year 2023 are also briefly described in the manuscript. Conclusion: This manuscript, describing the pharmacological aspects of eleven anticancer novel drug therapies approved by the FDA, shall serve as a helpful document for cancer patients, concerned academicians, researchers, and clinicians, especially oncologists.

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.

Background: Genetically altered recombinant poxviruses hold great therapeutic promise in animal models of cancer. Poxviruses can induce effective cellmediated immune responses against tumor-associated antigens. Preventive and therapeutic vaccination with a DNA vaccine expressing IL-13Rα2 can mediate partial regression of established tumors in vivo, indicating that host immune responses against IL-13Rα2 need further augmentation. Objective: The aim of the study is developing a recombinant modified vaccinia Ankara (MVA) expressing IL-13Rα2 (rMVA-IL13Rα2) virus and study in vitro infectivity and efficacy against IL-13Rα2 positive cell lines. Methods: We constructed a recombinant MVA expressing IL-13Rα2 and a green fluorescent protein (GFP) reporter gene. Purified virus titration by infection of target cells and immunostaining using anti-vaccinia and anti-IL-13Rα2 antibodies was used to confirm the identity and purity of the rMVA-IL13Rα2. Results: Western Blot analysis confirmed the presence of IL-13Rα2 protein (~52 kDa). Flow cytometric analysis of IL-13Rα2 negative T98G glioma cells when infected with rMVA-IL13Rα2 virus demonstrated cell-surface expression of IL-13Rα2, indicating the infectivity of the recombinant virus. Incubation of T98G-IL13Rα2 cells with varying concentrations (0.1-100 ng/ml) of interleukin-13 fused to truncated Pseudomonas exotoxin (IL13-PE) resulted in depletion of GFP⁺; fluorescence in T98G-IL13Rα2 cells. IL13-PE (10-1000 ng/ml) at higher concentrations also inhibited the protein synthesis in T98G-IL13Rα2 cells compared to cells infected with the control pLW44-MVA virus. IL13- PE treatment of rMVA-IL13Rα2 infected chicken embryonic fibroblast and DF-1 cell line reduced virus titer compared to untreated cells. Conclusion: rMVA-IL13Rα2 virus can successfully infect mammalian cells to express IL-13Rα2 in a biologically active form on the surface of infected cells. To evaluate the efficacy of rMVA-IL13Rα2, immunization studies are planned in murine tumor models.

Background: Angiopoietin-like protein 3 (ANGPTL-3) modulates lipid metabolism and the risk of coronary artery disease (CAD), especially stable angina (SA), via suppressing lipoprotein lipase (LPL). However, whether there are other mechanisms is not elucidated yet. The current research explored the modulatory roles of ANGPTL-3 on high-density lipoprotein (HDL), which further affects atherosclerotic development. Methods: A total of 200 individuals were enrolled in the present study. Serum ANGPTL- 3 levels were detected via enzyme-linked immunosorbent assays (ELISA). Cholesterol efflux capacity induced by HDL particles was detected through H³;-cholesterol loading THP-1 cell. Results: The serum ANGPTL-3 levels presented no significant discordance between the SA group and the non-SA group, whereas the serum ANGPTL-3 levels in type 2 diabetes mellitus (T2DM) group were significantly elevated compared with those in the non-T2DM group [428.3 (306.2 to 736.8) ng/ml vs. 298.2 (156.8 to 555.6) ng/ml, p <0.05]. Additionally, the serum ANGPTL-3 levels were elevated in patients with low TG levels compared to those in patients with high TG levels [519.9 (377.6 to 809.0) ng/ml vs. 438.7 (329.2 to 681.0) ng/ml, p <0.05]. By comparison, the individuals in the SA group and T2DM group presented decreased cholesterol efflux induced by HDL particles [SA: (12.21±2.11)% vs. (15.51±2.76)%, p <0.05; T2DM: (11.24±2.13)% vs. (14.65± 3.27)%, p <0.05]. In addition, the serum concentrations of ANGPTL-3 were inversely associated with the cholesterol efflux capacity of HDL particles (r=-0.184, p <0.05). Through regression analysis, the serum concentrations of ANGPTL-3 were found to be an independent modulator of the cholesterol efflux capacity of HDL particles (standardized β=-0.172, p <0.05). Conclusion: ANGPTL-3 exhibited a negative modulatory function on cholesterol efflux capacity induced by HDL particles.

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. Methods: 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. Results: 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: 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.

Background: To develop optimal personalized therapy for lung adenocarcinoma (LUAD), potential biomarkers associated with the prognosis are urgently needed. It is unclear what role T Cell Leukemia Homeobox 1 (TLX1) plays in LUAD. Objective: In this study, TLX1's relationship with LUAD was investigated using TCGA database analysis, bioinformatics analysis, and experimental validation. Methods: We examined the expression of TLX1 in pan cancer and LUAD, the relationship between TLX1 expression and clinical features, immune infiltration, its diagnostic and prognostic value, as well as TLX1 related pathways. The analysis included various statistical methods, including the Kaplan-Meier method, Cox regression analysis, GSEA, and immune infiltration analysis. TLX1 expression in LUAD cell lines was validated using qRT-PCR. Result: In LUAD patients, high expression of TLX1 was associated with T stage (P<0.001). High TLX1 expression was associated with worse overall survival (OS) (HR: 1.57; 95% CI: 1.18–2.1; P=0.002). And TLX1 HR: 1.619; 95% CI: 1.012-2.590; P=0.044) was independently correlated with OS in LUAD patients. TLX1 expression was associated with the pathways, including Rho GTPase effectors, DNA repair, TCF dependent signaling in response to WNT, signaling by Nuclear Receptors, signaling by Notch, chromatin-modifying enzymes, ESR-mediated signaling, cellular senescence, and transcriptional regulation by Runx1. TLX1 expression was correlated with aDC, Tcm, and TReg cells. The expression of TLX1 was significantly increased in LUAD cells compared to BEAS-2B cells. Conclusion: An association between high TLX1 expression and poor survival and immune infiltration was found in LUAD patients. There may be a potential role for TLX1 in diagnosis, prognosis, and immunotherapy for LUAD.

Background and objective: The novel marine factor 3,5-dihydroxy-4- methoxybenzyl alcohol (DHMBA) was originally identified in the Pacific oyster Crassostrea Gigas. DHMBA has been shown to prevent oxidative stress by scavenging radicals and enhance the production of antioxidant proteins. However, the pharmacologic role of DHMBA has been poorly understood. Inflammation is implicated in the pathogenesis of many diseases. Inflammatory cytokines are produced in macrophages with stimulation of lipopolysaccharide (LPS) and are used as biomarkers that cause diverse disease conditions. Therefore, this study has been undertaken to elucidate whether DHMBA expresses anti-inflammatory effects in in vitro mouse macrophage RAW264.7 cells. Methods: Mouse macrophage RAW264.7 cells were cultured in a medium containing 10% fetal bovine serum (FBS) with or without DHMBA (1-1000 μM). Results: Culturing with DHMBA (1-1000 μM) suppressed the growth and stimulated the death of RAW264.7 cells in vitro, leading to a decrease in cell number. Treatment with DHMBA reduced the levels of Ras, PI3K, Akt, MAPK, phospho-MAPK, and mTOR, which are signalling factors to promote cell proliferation, and it raised the levels of p53, p21, Rb, and regucalcin, which are cell growth suppressors. DHMBA treatment elevated caspase-3 and cleaved caspase-3 levels. Interestingly, DHMBA treatment repressed the production of inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, interleukin-1β, or prostaglandin E2, which were enhanced by LPS stimulation. Notably, the levels of NF-ΚB p65 were increased by LPS treatment, and this augmentation was repres-sed by DHMBA treatment. Moreover, LPS treatment stimulated osteoclastogenesis of RAW264.7 cells. This stimulation was blocked by DHMBA treatment, and this effect was not caused by the presence of an NF-ΚB signalling inhibitor. Conclusion: DHMBA was found to potentially suppress the activity of inflammatory macrophages in vitro, suggesting its therapeutic usefulness in inflammatory conditions.