Isolation and molecular characterization of lumpy skin disease virus from Tamil Nadu, India during the outbreaks from 2020 to 2022.

Lumpy skin disease (LSD) caused by LSD virus is a WOAH notifiable, high-impact, transboundary poxviral disease of bovines. The first official report of LSDV in India is from Odisha state during August 2019. Since then, cases have been reported from many states including Tamil Nadu, a Southern state of India. The present study deals with isolation and molecular characterization of LSDV from Tamil Nadu during the period August 2020 to July 2022. LSDV was isolated in embryonated chicken eggs (ECE) and BHK 21 cells and was characterized based on P32, RPO30, and GPCR genes. The phylogenetic analysis revealed that Tamil Nadu isolates from India are closely related to other Indian strains, Kenyan strains and strains from neighboring countries such as Bangladesh, Nepal, and Myanmar confirming the common exotic source for the transboundary spread across borders. The presence of unique signature of amino acid (aa) at specific positions (A11, T12, T34, S99, and P199) in the GPCR sequence confirmed the identity of LSDV. A twelve nucleotide (nt94-105) insertion and corresponding aa (TILS) at 30-33 position was found in GPCR sequence and characteristic amino acid proline at 98 position (P98) in the RPO30 gene sequence of our isolates was similar to strains from Bangladesh, Nepal, and Myanmar. Further, dissimilarity of our isolates from Neethling like vaccine strains confirms the circulation of virulent filed strains responsible for the outbreaks.

A comprehensive and systemic review of ginseng-based nanomaterials: Synthesis, targeted delivery, and biomedical applications.

Among 17 Panax species identified across the world, Panax ginseng (Korean ginseng), Panax quinquefolius (American ginseng), and Panax notoginseng (Chinese ginseng) are highly recognized for the presence of bioactive compound, ginsenosides and their pharmacological effects. P. ginseng is widely used for synthesis of different types of nanoparticles compared to P. quinquefolius and P. notoginseng. The use of nano-ginseng could increase the oral bioavailability, membrane permeability, and thus provide effective delivery of ginsenosides to the target sites through transport system. In this review, we explore the synthesis of ginseng nanoparticles using plant extracts from various organs, microbes, and polymers, as well as their biomedical applications. Furthermore, we highlight transporters involved in transport of ginsenoside nanoparticles to the target sites. Size, zeta potential, temperature, and pH are also discussed as the critical parameters affecting the quality of ginseng nanoparticles synthesis.

Potential of chimeric antigen receptor (CAR)-redirected immune cells in breast cancer therapies: Recent advances.

Despite substantial developments in conventional treatments such as surgery, chemotherapy, radiotherapy, endocrine therapy, and molecular-targeted therapy, breast cancer remains the leading cause of cancer mortality in women. Currently, chimeric antigen receptor (CAR)-redirected immune cell therapy has emerged as an innovative immunotherapeutic approach to ameliorate survival rates of breast cancer patients by eliciting cytotoxic activity against cognate tumour-associated antigens expressing tumour cells. As a crucial component of adaptive immunity, T cells and NK cells, as the central innate immune cells, are two types of pivotal candidates for CAR engineering in treating solid malignancies. However, the biological distinctions between NK cells- and T cells lead to differences in cancer immunotherapy outcomes. Likewise, optimal breast cancer removal via CAR-redirected immune cells requires detecting safe target antigens, improving CAR structure for ideal immune cell functions, promoting CAR-redirected immune cells filtration to the tumour microenvironment (TME), and increasing the ability of these engineered cells to persist and retain within the immunosuppressive TME. This review provides a concise overview of breast cancer pathogenesis and its hostile TME. We focus on the CAR-T and CAR-NK cells and discuss their significant differences. Finally, we deliver a summary based on recent advancements in the therapeutic capability of CAR-T and CAR-NK cells in treating breast cancer.

A comprehensive review of IL-26 to pave a new way for a profound understanding of the pathobiology of cancer, inflammatory diseases and infections.

Cytokines are considered vital mediators of the immune system. Down- or upregulation of these mediators is linked to several inflammatory and pathologic situations. IL-26 is referred to as an identified member of the IL-10 family and IL-20 subfamily. Due to having a unique cationic structure, IL-26 exerts diverse functions in several diseases. Since IL-26 is mainly secreted from Th17, it is primarily considered a pro-inflammatory cytokine. Upon binding to its receptor complex (IL-10R1/IL-20R2), IL-26 activates multiple signalling mediators, especially STAT1/STAT3. In cancer, IL-26 induces IL-22-producing cells, which consequently decrease cytotoxic T-cell functions and promote tumour growth through activating anti-apoptotic proteins. In hypersensitivity conditions such as rheumatoid arthritis, multiple sclerosis, psoriasis and allergic disease, this cytokine functions primarily as the disease-promoting mediator and might be considered a biomarker for disease prognosis. Although IL-26 exerts antimicrobial function in infections such as hepatitis, tuberculosis and leprosy, it has also been shown that IL-26 might be involved in the pathogenesis and exacerbation of sepsis. Besides, the involvement of IL-26 has been confirmed in other conditions, including graft-versus-host disease and chronic obstructive pulmonary disease. Therefore, due to the multifarious function of this cytokine, it is proposed that the underlying mechanism regarding IL-26 function should be elucidated. Collectively, it is hoped that the examination of IL-26 in several contexts might be promising in predicting disease prognosis and might introduce novel approaches in the treatment of various diseases.

Does CCL19 act as a double-edged sword in cancer development?

Cancer is considered a life-threatening disease, and several factors are involved in its development. Chemokines are small proteins that physiologically exert pivotal roles in lymphoid and non-lymphoid tissues. The imbalance or dysregulation of chemokines has contributed to the development of several diseases, especially cancer. CCL19 is one of the homeostatic chemokines that is abundantly expressed in the thymus and lymph nodes. This chemokine, which primarily regulates immune cell trafficking, is involved in cancer development. Through the induction of anti-tumor immune responses and inhibition of angiogenesis, CCL19 exerts tumor-suppressive functions. In contrast, CCL19 also acts as a tumor-supportive factor by inducing inflammation, cell growth, and metastasis. Moreover, CCL19 dysregulation in several cancers, including colorectal, breast, pancreatic, and lung cancers, has been considered a tumor biomarker for diagnosis and prognosis. Using CCL19-based therapeutic approaches has also been proposed to overcome cancer development. This review will shed more light on the multifarious function of CCL19 in cancer and elucidate its application in diagnosis, prognosis, and even therapy. It is expected that the study of CCL19 in cancer might be promising to broaden our knowledge of cancer development and might introduce novel approaches in cancer management.

Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora.

In recent years, there has been a greater emphasis on the impact of microbial populations inhabiting the gastrointestinal tract on human health and disease. According to the involvement of microbiota in modulating physiological processes (such as immune system development, vitamins synthesis, pathogen displacement, and nutrient uptake), any alteration in its composition and diversity (i.e., dysbiosis) has been linked to a variety of pathologies, including cancer. In this bidirectional relationship, colonization with various bacterial species is correlated with a reduced or elevated risk of certain cancers. Notably, the gut microflora could potentially play a direct or indirect role in tumor initiation and progression by inducing chronic inflammation and producing toxins and metabolites. Therefore, identifying the bacterial species involved and their mechanism of action could be beneficial in preventing the onset of tumors or controlling their advancement. Likewise, the microbial community affects anti-cancer approaches' therapeutic potential and adverse effects (such as immunotherapy and chemotherapy). Hence, their efficiency should be evaluated in the context of the microbiome, underlining the importance of personalized medicine. In this review, we summarized the evidence revealing the microbiota's involvement in cancer and its mechanism. We also delineated how microbiota could predict colon carcinoma development or response to current treatments to improve clinical outcomes.

Biological causes of immunogenic cancer cell death (ICD) and anti-tumor therapy; Combination of Oncolytic virus-based immunotherapy and CAR T-cell therapy for ICD induction.

Chimeric antigen receptor (CAR) T-cell therapy is a promising and rapidly expanding therapeutic option for a wide range of human malignancies. Despite the ongoing progress of CAR T-cell therapy in hematologic malignancies, the application of this therapeutic strategy in solid tumors has encountered several challenges due to antigen heterogeneity, suboptimal CAR T-cell trafficking, and the immunosuppressive features of the tumor microenvironment (TME). Oncolytic virotherapy is a novel cancer therapy that employs competent or genetically modified oncolytic viruses (OVs) to preferentially proliferate in tumor cells. OVs in combination with CAR T-cells are promising candidates for overcoming the current drawbacks of CAR T-cell application in tumors through triggering immunogenic cell death (ICD) in cancer cells. ICD is a type of cellular death in which danger-associated molecular patterns (DAMPs) and tumor-specific antigens are released, leading to the stimulation of potent anti-cancer immunity. In the present review, we discuss the biological causes of ICD, different types of ICD, and the synergistic combination of OVs and CAR T-cells to reach potent tumor-specific immunity.

Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons.

The main breakthrough in tumor immunotherapy was the discovery of immune checkpoint (IC) proteins, which act as a potent suppressor of the immune system by a myriad of mechanisms. After that, scientists focused on the immune checkpoint molecules mainly. Thereby, much effort was spent to progress novel strategies for suppressing these inhibitory axes, resulting in the evolution of immune checkpoint inhibitors (ICIs). Then, ICIs have become a promising approach and shaped a paradigm shift in tumor immunotherapies. CTLA-4 plays an influential role in attenuation of the induction of naïve and memory T cells by engagement with its responding ligands like B7-1 (CD80) and B7-2 (CD86). Besides, PD-1 is predominantly implicated in adjusting T cell function in peripheral tissues through its interaction with programmed death-ligand 1 (PD-L1) and PD-L2. Given their suppressive effects on anti-tumor immunity, it has firmly been documented that ICIs based therapies can be practical and rational therapeutic approaches to treat cancer patients. Nonetheless, tumor inherent or acquired resistance to ICI and some treatment-related toxicities restrict their application in the clinic. The current review will deliver a comprehensive overview of the ICI application to treat human tumors alone or in combination with other modalities to support more desired outcomes and lower toxicities in cancer patients. Video Abstract.

A comprehensive review about immune responses and exhaustion during coronavirus disease (COVID-19).

Coronavirus disease (COVID-19) is a viral infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The infection was reported in Wuhan, China, in late December 2019 and has become a major global concern due to severe respiratory infections and high transmission rates. Evidence suggests that the strong interaction between SARS-CoV-2 and patients' immune systems leads to various clinical symptoms of COVID-19. Although the adaptive immune responses are essential for eliminating SARS-CoV-2, the innate immune system may, in some cases, cause the infection to progress. The cytotoxic CD8+ T cells in adaptive immune responses demonstrated functional exhaustion through upregulation of exhaustion markers. In this regard, humoral immune responses play an essential role in combat SARS-CoV-2 because SARS-CoV-2 restricts antigen presentation through downregulation of MHC class I and II molecules that lead to the inhibition of T cell-mediated immune response responses. This review summarizes the exact pathogenesis of SARS-CoV-2 and the alteration of the immune response during SARS-CoV-2 infection. In addition, we've explained the exhaustion of the immune system during SARS-CoV-2 and the potential immunomodulation approach to overcome this phenomenon. Video Abstract.

Anastasis: cell recovery mechanisms and potential role in cancer.

Balanced cell death and survival are among the most important cell development and homeostasis pathways that can play a critical role in the onset or progress of malignancy steps. Anastasis is a natural cell recovery pathway that rescues cells after removing the apoptosis-inducing agent or brink of death. The cells recuperate and recover to an active and stable state. So far, minimal knowledge is available about the molecular mechanisms of anastasis. Still, several involved pathways have been explained: recovery through mitochondrial outer membrane permeabilization, caspase cascade arrest, repairing DNA damage, apoptotic bodies formation, and phosphatidylserine. Anastasis can facilitate the survival of damaged or tumor cells, promote malignancy, and increase drug resistance and metastasis. Here, we noted recently known mechanisms of the anastasis process and underlying molecular mechanisms. Additionally, we summarize the consequences of anastatic mechanisms in the initiation and progress of malignancy, cancer cell metastasis, and drug resistance. Video Abstract.

Exploring the role of antibiotics and steroids in managing respiratory diseases.

Respiratory diseases (RDs), such as chronic obstructive pulmonary disease, cystic fibrosis, asthma, and pneumonia, are associated with significant morbidity and mortality. Treatment usually consists of antibiotics and steroids. Relevant published literature reviews, studies, and clinical trials were accessed from institutional and electronic databases. The keywords used were respiratory diseases, steroids, antibiotics, and combination of steroids and antibiotics. Selected articles and literature were carefully reviewed. Antibiotics are often prescribed as the standard therapy to manage RDs. Types of causative respiratory pathogens, spectrum of antibiotics activity, route of administration, and course of therapy determine the type of antibiotics that are prescribed. Despite being associated with good clinical outcome, treatment failure and recurrence rate are still high. In addition, antibiotic resistance has been widely reported due to bacterial mutations in response to the use of antibiotics, which render them ineffective. Nevertheless, there has been a growing demand for corticosteroids (CS) and antibiotics to treat a wide variety of diseases, including various airway diseases, due to their immunosuppressive and anti-inflammatory properties. The use of CS is well established and there are different formulations based on the diseases, such as topical administration, tablets, intravenous injections, and inhaled preparations. Both antibiotics and CS possess similar properties in terms of their anti-inflammatory effects, especially regulating cytokine release. Thus, the current review examines and discusses the different applications of antibiotics, CS, and their combination in managing various RDs. Drawbacks of these interventions are also discussed.

Nutrient pattern analysis of mineral based, simple sugar based, and fat based diets and risk of metabolic syndrome: a comparative nutrient panel.

BACKGROUND: Although there is growing evidence on the association between nutrient patterns and metabolic risk factors, very little is known about the relationship between nutrient patterns and metabolic syndrome (MetS). The aim of this study was to examine the associations of nutrient patterns with MetS among apparently healthy obese adults living in Tabriz, Iran. METHODS: Three hundred and forty-seven apparently healthy obese (BMI ≥ 30 kg/m2) adults aged 20-50 years were included in this cross-sectional study. Dietary intake of 38 nutrients was assessed by a validated semi-quantitative food frequency questionnaire (FFQ) of 132 food items. Nutrient patterns were determined using factor analysis. The MetS was defined based on the guidelines of the National Cholesterol Education Program Adult Treatment Panel III (ATP III). RESULTS: Three major nutrient patterns were extracted: "Mineral based pattern", "Simple sugar based pattern" and "Fat based pattern". There was no significant association between nutrient patterns and MetS, in the crude model even after adjusting for confounders. There was a significant difference between quartiles in the mineral based pattern for free mass (FFM), diastolic blood pressure (DBP), large Waist circumference (WC) and Waist-to-hip ratio (WHR). In the simple sugar based pattern, we observed a significant association for SBP, DBP, and triglyceride (TG) levels. In addition, the fat based pattern was positively associated with BMI, and weight. CONCLUSIONS: We did not observe any significant association of nutrient patterns with the risk of MetS amongst the apparently healthy obese adult's population. Whereas we confirmed the deleterious effect of the simple sugar and fat based patterns on several metabolic risk factors, our findings also showed that the mineral based pattern is related to healthier metabolic factors in an Iranian population. These results should be approved by future studies to recognize any causal relationship between adherence to specific nutrient patterns and MetS.

Therapeutic utility of mesenchymal stromal cell (MSC)-based approaches in chronic neurodegeneration: a glimpse into underlying mechanisms, current status, and prospects.

Recently, mesenchymal stromal cell (MSC)-based therapy has become an appreciated therapeutic approach in the context of neurodegenerative disease therapy. Accordingly, a myriad of studies in animal models and also some clinical trials have evinced the safety, feasibility, and efficacy of MSC transplantation in neurodegenerative conditions, most importantly in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). The MSC-mediated desired effect is mainly a result of secretion of immunomodulatory factors in association with release of various neurotrophic factors (NTFs), such as glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF). Thanks to the secretion of protein-degrading molecules, MSC therapy mainly brings about the degradation of pathogenic protein aggregates, which is a typical appearance of chronic neurodegenerative disease. Such molecules, in turn, diminish neuroinflammation and simultaneously enable neuroprotection, thereby alleviating disease pathological symptoms and leading to cognitive and functional recovery. Also, MSC differentiation into neural-like cells in vivo has partially been evidenced. Herein, we focus on the therapeutic merits of MSCs and also their derivative exosome as an innovative cell-free approach in AD, HD, PD, and ALS conditions. Also, we give a brief glimpse into novel approaches to potentiate MSC-induced therapeutic merits in such disorders, most importantly, administration of preconditioned MSCs.

The effect of flaxseed oil consumtion on blood pressure among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized clinical trials.

We systematically reviewed randomized clinical trials (RCTs) to elucidate the overall effects of flaxseed oil consumption on blood pressure (BP) in patients with metabolic syndrome and related disorders. PubMed, Scopus, Cochrane Library, and ISI Web of Science databases were systematically searched until March 31, 2020, to find RCTs that examined the effect of flaxseed oil consumption on BP. Weighed mean difference (WMD) was pooled using a random-effects model. Standard methods were used for the assessment of heterogeneity, sensitivity analysis, and publication bias. Meta-analysis of five trials (6 arms) showed significant reductions in systolic (WMD: -3.86 mmHg, 95% CI: -7.59 to -0.13, p = .04) BP (SBP) after flaxseed oil consumption. However, the overall effect illustrated no significant change in diastolic (WMD: -1.71 mmHg, 95% CI: -3.67 to 0.26, p = .09) BP (DBP) in the intervention group compared with the control group. Our findings revealed that flaxseed oil consumption has favorable effects on SBP in patients with metabolic syndrome and related disorders. However, further investigations are needed to provide more reliable evidence.

Acacia catechu seed extract provokes cytotoxicity via apoptosis by intrinsic pathway in HepG2 cells.

Acacia catechu Willd (Fabaceae) is a thorny tree widely distributed in India and commonly used as traditional Ayurvedic medicine for various ailments. The current study evaluates the cytotoxic potentials of A. catechu ethanolic seed extract (ACSE) in HepG2 cells, a human hepatocellular carcinoma cell line. The HepG2 cells were treated with 0.1, 0.3, 1, 3, 10, 30, 100, 300 and 1000 µg/ml of ACSE and the cytotoxic effect was evaluated by MTT and lactate dehydrogenase (LDH) leakage assays. The IC50 of ACSE was found at 77.04 µg/ml and therefore, further studies were carried out with the concentrations of 35 and 70 µg/ml. The intracellular reactive oxygen species (ROS) generation and apoptosis-related morphological changes were evaluated. Gene expressions of Bax, Bcl-2, cytochrome C (Cyt-c), caspases-9 and 3 were analyzed by qPCR. The ACSE treatments caused LDH leakage was associated with an increased ROS generation. The increased ROS generation was associated with the downregulation of intracellular antioxidant enzyme superoxide dismutase and reduced glutathione content. AO/EB and PI staining also confirmed chromatin condensation and apoptosis. The flow cytometric analysis showed an accumulation of HepG2 cells at sub G0/G1 (apoptotic) phase upon ACSE treatments. The ACSE induced cytotoxicity and oxidative stress were related to increased apoptotic marker gene expressions such as Bax, Cyt-c, caspase-9 and 3, and decreased anti-apoptotic marker Bcl-2. The current finding suggests that ACSE has apoptosis-inducing potential via the mitochondrial pathway in HepG2 cells.

Compositional profile of mucosal bacteriome of smokers and smokeless tobacco users.

INTRODUCTION: Smoked, and especially smokeless, tobacco are major causes of oral cancer globally. Here, we examine the oral bacteriome of smokers and of smokeless tobacco users, in comparison to healthy controls, using 16S rRNA gene sequencing. METHODS: Oral swab samples were collected from smokers, smokeless tobacco users, and healthy controls (n = 44). Microbial DNA was extracted and the 16S rRNA gene profiled using the Illumina MiSeq platform. Sequencing reads were processed using DADA2, and taxonomical classification was performed using the phylogenetic placement method. Differentially abundant taxa were identified using DESeq2, while functional metagenomes based on KEGG orthology abundance were inferred using LIMMA. RESULTS: A significantly higher microbial diversity was observed in smokeless tobacco users and smokers relative to controls (P < 0.05). Compositional differences in microbial communities were observed in all comparisons with healthy controls (PERMANOVA P < 0.05) but not between smokers and smokeless tobacco users. Levels of Fusobacterium spp., Saccharibacterium spp., and members of Shuttleworthia were elevated in smokers when compared to controls (BH adj P < 0.01). In addition, the relative abundance of three bacterial taxa belonging to genera Fusobacterium spp., Catonella, and Fretibacterium spp. was significantly increased in smokeless tobacco users relative to controls (BH adj P < 0.01). Major functional pathways significantly increased in smokeless tobacco users relative to both controls, and smokers were similar and involved amino acid metabolism including glutamate and aspartate biosynthesis and degradation (log FC > 1.5; BH adj P < 0.01). CONCLUSIONS: A distinct taxonomic and functional profile of oral microbiome in smokers and smokeless tobacco users as compared to healthy controls implicates a significant role of microbes and their metabolites in diseases associated with tobacco use including oral cancer. CLINICAL RELEVANCE: Future efforts in preventive, diagnostic, curative, and prognostic strategies for diseases associated with tobacco use in smokers and smokeless tobacco users could incorporate the oral microbiome.

Intimate partner violence against pregnant women during the COVID-19 pandemic: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to estimate the pooled prevalence of (intimate partner violence) IPV against pregnant women in the COVID-19 pandemic. A literature search was conducted in PubMed, Web of Science, and Scopus for observational studies regarding the prevalence of IPV against pregnant women during the COVID-19 pandemic. The search was performed with the following keywords: intimate partner violence, domestic violence, battered women, wife assault, partner assault, wife abuse, partner abuse, femicide, domestic homicide, pregnancy, gestation, pregnant women, COVID-19, SARS-CoV-2, 2019-nCoV, Coronavirus Disease-19, 2019 Novel Coronavirus, Wuhan Coronavirus, SARS Coronavirus 2, Wuhan Seafood Market Pneumonia Virus. Heterogeneity between the studies was assessed using Cochran's Q test and I2 index. In addition, a random-effects model was used to estimate the prevalence of IPV. Data analysis was performed in Stata software version 16. Six articles met our inclusion criteria, which were conducted on 2213 pregnant women. The pooled prevalence of total IPV was estimated at 22 percent (95 percent Confidence Interval [CI]: 4-40 percent). Moreover, the pooled prevalence of psychological, physical, and sexual violence was reported to be 24 percent (95 percent CI: 13-35 percent), 14 percent (95 percent CI: 7-20 percent), and 6 percent (95 percent CI: 4-9 percent), respectively. Publication bias was significant (P = .01). According to the results, IPV against pregnant women has been relatively prevalent during the COVID-19 pandemic. Therefore, identifying the women who are at the risk of IPV is essential to preventing the consequences of maternal-fetal abuse and designing strategies to facilitate the reporting of violence during pandemics.

Biphasic Functions of Sodium Fluoride (NaF) in Soft and in Hard Periodontal Tissues.

Sodium fluoride (NaF) is widely used in clinical dentistry. However, the administration of high or low concentrations of NaF has various functions in different tissues. Understanding the mechanisms of the different effects of NaF will help to optimize its use in clinical applications. Studies of NaF and epithelial cells, osteoblasts, osteoclasts, and periodontal cells have suggested the significant roles of fluoride treatment. In this review, we summarize recent studies on the biphasic functions of NaF that are related to both soft and hard periodontal tissues, multiple diseases, and clinical dentistry.

Tilianin: A Potential Natural Lead Molecule for New Drug Design and Development for the Treatment of Cardiovascular Disorders.

Cardiovascular disorders (CVDs) are the leading risk factor for death worldwide, and research into the processes and treatment regimens has received a lot of attention. Tilianin is a flavonoid glycoside that can be found in a wide range of medicinal plants and is most commonly obtained from Dracocephalum moldavica. Due to its extensive range of biological actions, it has become a well-known molecule in recent years. In particular, numerous studies have shown that tilianin has cardioprotective properties against CVDs. Hence, this review summarises tilianin's preclinical research in CVDs, as well as its mechanism of action and opportunities in future drug development. The physicochemical and drug-likeness properties, as well as the toxicity profile, were also highlighted. Tilianin can be a natural lead molecule in the therapy of CVDs such as coronary heart disease, angina pectoris, hypertension, and myocardial ischemia, according to scientific evidence. Free radical scavenging, inflammation control, mitochondrial function regulation, and related signalling pathways are all thought to play a role in tilianin's cardioprotective actions. Finally, we discuss tilianin-derived compounds, as well as the limitations and opportunities of using tilianin as a lead molecule in drug development for CVDs. Overall, the scientific evidence presented in this review supports that tilianin and its derivatives could be used as a lead molecule in CVD drug development initiatives.

Kirenol: A Potential Natural Lead Molecule for a New Drug Design, Development, and Therapy for Inflammation.

Kirenol, a potential natural diterpenoid molecule, is mainly found in Sigesbeckia species. Kirenol has received a lot of interest in recent years due to its wide range of pharmacological actions. In particular, it has a significant ability to interact with a wide range of molecular targets associated with inflammation. In this review, we summarise the efficacy and safety of kirenol in reducing inflammation, as well as its potential mechanisms of action and opportunities in future drug development. Based on the preclinical studies reported earlier, kirenol has a good therapeutic potential against inflammation involved in multiple sclerosis, inflammatory bowel disorders, diabetic wounds, arthritis, cardiovascular disease, bone damage, and joint disorders. We also address the physicochemical and drug-like features of kirenol, as well as the structurally modified kirenol-derived molecules. The inhibition of pro-inflammatory cytokines, reduction in the nuclear factor kappa-B (NF-κB), attenuation of antioxidant enzymes, stimulation of heme-oxygenase-1 (HO-1) expression, and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation are among the molecular mechanisms contributing to kirenol's anti-inflammatory actions. Furthermore, this review also highlights the challenges and opportunities to improve the drug delivery of kirenol for treating inflammation. According to the findings of this review, kirenol is an active molecule against inflammation in numerous preclinical models, indicating a path to using it for new drug discovery and development in the treatment of a wide range of inflammations.