The recent discovery of a promising pharmacological scaffold derived from carvacrol: A review.

Carvacrol, called CA, is a dynamic phytoconstituent characterized by a phenol ring abundantly sourced from various natural reservoirs. This versatile scaffold serves as a pivotal template for the design and synthesis of novel drug molecules, harboring promising biological activities. The active sites positioned at C-4, C-6, and the hydroxyl group (-OH) of CA offer fertile ground for creating potent drug candidates from a pharmacological standpoint. In this comprehensive review, we delve into diverse synthesis pathways and explore the biological activity of CA derivatives. We aim to illuminate the potential of these derivatives in discovering and developing efficacious treatments against a myriad of life-threatening diseases. By scrutinizing the structural modifications and pharmacophore placements that enhance the activity of CA derivatives, we aspire to inspire the innovation of novel therapeutics with heightened potency and effectiveness.

Piper sarmentosum Roxb. Inhibits Angiotensin-Converting Enzyme Activity in Phorbol 12-Myristate-13-Acetate-Induced Endothelial Cells.

Angiotensin-converting enzyme (ACE) plays a crucial role in the pathogenesis of hypertension. Piper sarmentosum Roxb., an herb known for its antihypertensive effect, lacks a comprehensive understanding of the mechanism underlying its antihypertensive action. This study aimed to elucidate the antihypertensive mechanism of aqueous extract of P. sarmentosum leaves (AEPS) via its modulation of the ACE pathway in phorbol 12-myristate-13-acetate (PMA)-induced human umbilical vein endothelial cells (HUVECs). HUVECs were divided into five groups: control, treatment with 200 µg/mL AEPS, induction 200 nM PMA, concomitant treatment with 200 nM PMA and 200 µg/mL AEPS, and treatment with 200 nM PMA and 0.06 µM captopril. Subsequently, ACE mRNA expression, protein level and activity, angiotensin II (Ang II) levels, and angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) mRNA expression in HUVECs were determined. AEPS successfully inhibited ACE mRNA expression, protein and activity, and angiotensin II levels in PMA-induced HUVECs. Additionally, AT1R expression was downregulated, whereas AT2R expression was upregulated. In conclusion, AEPS reduces the levels of ACE mRNA, protein and activity, Ang II, and AT1R expression in PMA-induced HUVECs. Thus, AEPS has the potential to be developed as an ACE inhibitor in the future.

Smoking and Unstable Plaque in Acute Coronary Syndrome: A Systematic Review of The Role of Matrix Metalloproteinases.

Smoking is a risk factor of acute coronary syndrome (ACS) that could increase matrix metalloproteinases (MMPs) levels, leading to unstable coronary artery plaque. The current review aimed to identify the relationship between smoking and MMPs in patients with ACS. Literature search was conducted from inception until March 2022 in three online databases. Risk of bias was assessed using the Newcastle-Ottawa Scale. A meta-analysis was performed, and the odds ratio (OR) together with its 95% confidence interval (CI) were determined. A total of 7,843 articles were identified, and only seven studies were included. Four studies investigated the MMP-3 and MMP-9 related genes and found that smokers with certain MMPs genotypes had high risk of ACS. Smoking also increased the MMPs level in patients with ACS compared with non-smokers. Additionally, a meta-analysis of two studies resulted in an increased odd of ACS in smokers with MMP-3 5A allele versus non-smokers with MMP-3 6A6A allele (OR: 15.94, 95% CI: 10.63-23.92; I2 =55%). In conclusion, the current review highlights the role of MMPs in relation to smoking and ACS. The determination of these roles may help in identifying new ACS markers among smokers and the development of drug-targeted treatment.

Role of Matrix Metalloproteinase-2 in the Development of Atherosclerosis among Patients with Coronary Artery Disease.

Coronary artery disease (CAD) is a caused by atherosclerotic plaque buildup in the coronary arteries that supply blood and oxygen to the heart. Matrix metalloproteinase (MMP) is a family of zinc-dependent endopeptidase that is involved in various stages of atherosclerosis as demonstrated in in vitro and in vivo studies. MMP-2 is associated with both stable and unstable atherosclerotic plaque formation. The current review aimed to identify the role of MMP-2 in atherosclerosis development among CAD patients. Literature search was conducted through four online databases and only studies that were published from 2018 until February 2023 were included. The risk of bias was assessed by using the Newcastle-Ottawa Scale. A total of 10,622 articles were initially identified, and only eight studies that fulfilled the selection criteria were included in this review. The results showed that MMP-2 levels and activity were higher in patients with unstable CAD than those with stable CAD and healthy subjects. There was a significant association between MMP-2 levels and cardiovascular disease with MMP-14 levels, which is a pro-MMP-2 activator. In addition, two single nucleotide polymorphisms of the MMP-2 gene (rs243865 and rs243866) were significantly associated with the development of atherosclerosis. In conclusion, MMP-2 plays a crucial role in the development of atherosclerosis among patients with CAD and could be a potential target for CAD therapy.

Role of Terpenophenolics in Modulating Inflammation and Apoptosis in Cardiovascular Diseases: A Review.

One in every three deaths worldwide is caused by cardiovascular diseases (CVDs), estimating a total of 17.9 million deaths annually. By 2030, it is expected that more than 24 million people will die from CVDs related complications. The most common CVDs are coronary heart disease, myocardial infarction, stroke, and hypertension. A plethora of studies has shown inflammation causing both short-term and long-term damage to the tissues in many organ systems, including the cardiovascular system. In parallel to inflammation processes, it has been discovered that apoptosis, a mode of programmed cell death, may also contribute to CVD development due to the loss of cardiomyocytes. Terpenophenolic compounds are comprised of terpenes and natural phenols as secondary metabolites by plants and are commonly found in the genus Humulus and Cannabis. A growing body of evidence has shown that terpenophenolic compounds exhibit protective properties against inflammation and apoptosis within the cardiovascular system. This review highlights the current evidence elucidating the molecular actions of terpenophenolic compounds in protecting the cardiovascular system, i.e., bakuchiol, ferruginol, carnosic acid, carnosol, carvacrol, thymol and hinokitiol. The potential of these compounds is discussed as the new nutraceutical drugs that may help to decrease the burden of cardiovascular disorders.

Nicotine Impairs the Anti-Contractile Function of Perivascular Adipose Tissue by Inhibiting the PPARγ-Adiponectin-AdipoR1 Axis.

Nicotine is an addictive compound found in cigarette smoke that leads to vascular dysfunction and cardiovascular diseases. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the underlying vasculature through the production of adipokines, such as adiponectin, which acts on adiponectin receptors 1 (adipoR1) to cause vasorelaxation. Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor that regulates adiponectin gene expression and PVAT development. This study aimed to determine the effect of nicotine on the anti-contractile function of PVAT via the PPARγ-adiponectin-adipoR1 axis. Male Sprague Dawley rats were divided into a control group (given normal saline), a nicotine group (given 0.8 mg/kg of nicotine), and a nicotine + PPARγ agonist group (given nicotine and 5 mg/kg of telmisartan). Thoracic aorta PVAT was harvested after 21 days of treatment. The results showed that nicotine reduced the anti-contractile effect of PVAT on the underlying thoracic aorta. Nicotine also decreased the gene and protein expression of PPARγ, adiponectin, and adipoR1 in PVAT. Treatment with telmisartan restored the anti-contractile effect of PVAT and increased the gene and protein expression of PPARγ, adiponectin, and adipoR1 in PVAT. In conclusion, nicotine attenuates the anti-contractile function of PVAT through inhibition of the PPARγ-adiponectin-adipoR1 axis.

Potential Roles of microRNAs for Assessing Cardiovascular Risk in Pre-Eclampsia-Exposed Postpartum Women and Offspring.

Pre-eclampsia, which is part of the spectrum of hypertensive pregnancy disorders, poses a significant health burden, contributing to maternal and infant morbidity and mortality. Pre-eclampsia is widely associated with persistent adverse effects on the cardiovascular health of women with a history of pre-eclampsia. Additionally, there is increasing evidence demonstrating that offspring of pre-eclamptic pregnancies have altered cardiac structure and function, as well as different vascular physiology due to the decrease in endothelial function. Therefore, early detection of the likelihood of developing pre-eclampsia-associated cardiovascular diseases is vital, as this could facilitate the undertaking of the necessary clinical measures to avoid disease progression. The utilisation of microRNAs as biomarkers is currently on the rise as microRNAs have been found to play important roles in regulating various physiological and pathophysiological processes. In regard to pre-eclampsia, recent studies have shown that the expression of microRNAs is altered in postpartum women and their offspring who have been exposed to pre-eclampsia, and that these alterations may persist for several years. This review, therefore, addresses changes in microRNA expression found in postpartum women and offspring exposed to pre-eclampsia, their involvement in cardiovascular disease, and the potential role of microRNAs to be used as predictive tools and therapeutic targets in future cardiovascular disease research.

Hyperandrogenism and Its Possible Effects on Endometrial Receptivity: A Review.

Endometrial receptivity is a state of the endometrium defined by its readiness for embryo implantation. When the receptivity of the endometrium is impaired due to hyperandrogenism or androgen excess, this condition can lead to pregnancy loss or infertility. Hyperandrogenism encompasses a wide range of clinical manifestations, including polycystic ovary syndrome (PCOS), idiopathic hirsutism, hirsutism and hyperandrogaenemia, non-classical congenital adrenal hyperplasia, hyperandrogenism, insulin resistance, acanthosis nigricans (HAIR-AN), ovarian or adrenal androgen-secreting neoplasms, Cushing's syndrome, and hyperprolactinaemia. Recurrent miscarriages have been shown to be closely related to elevated testosterone levels, which alter the endometrial milieu so that it is less favourable for embryo implantation. There are mechanisms for endometrial receptivity that are affected by excess androgen. The HOXA gene, aVß3 integrin, CDK signalling pathway, MECA-79, and MAGEA-11 were the genes and proteins affect endometrial receptivity in the presence of a hyperandrogenic state. In this review, we would like to explore the other manifestations of androgen excess focusing on causes other than PCOS and learn possible mechanisms of endometrial receptivity behind androgen excess leading to pregnancy loss or infertility.

Expression of HOXA10 Gene in Women with Endometriosis: A Systematic Review.

The homeobox A10 (HOXA10) gene is known to be related to endometriosis; however, due to a lack of knowledge/evidence in the pathogenesis of endometriosis, the mechanisms that link HOXA10 to endometriosis still need to be clarified. This review addresses the difference in the expression of the HOXA10 gene in endometriotic women versus non-endometriotic women across populations by country and discusses its influences on women's fertility. An organized search of electronic databases was conducted in Scopus, ScienceDirect, PubMed, and Web of Science. The keywords used were (HOXA10 OR "homeobox A10" OR PL OR HOX1 OR HOX1H OR HOX1.8) AND ("gene expression") AND (endometriosis). The initial search resulted in 623 articles, 10 of which were included in this review. All ten papers included in this study were rated fair in terms of the quality of the studies conducted. The expression of the HOXA10 gene was found to be downregulated in most studies. However, one study provided evidence of the downregulation and upregulation of HOXA10 gene expression due to the localization of endometriotic lesions. Measuring the expression of the HOXA10 gene in women is clinically essential to predicting endometriosis, endometrial receptivity, and the development of pinopodes in the endometrium during the luteal phase.

Revisiting miRNA-21 as a Therapeutic Strategy for Myocardial Infarction: A Systematic Review.

ABSTRACT: Several types of cardiovascular cells use microRNA-21 ( miR-21 ), which has been linked to cardioprotection. In this study, we systematically reviewed the results of published papers on the therapeutic effect of miR-21 for myocardial infarction. Studies described the cardioprotective effects of miR-21 to reduce infarct size by improving angiogenesis, antiapoptotic, and anti-inflammatory mechanisms. Results suggest that cardioprotective effects of miR-21 may work synergistically to prevent the deterioration of cardiac function during postischemia. However, there are other results that indicate that miR-21 positively regulates tissue fibrosis, potentially worsening a postischemic injury. The dual functionalities of miR-21 occur through the targeting of genes and signaling pathways, such as PTEN , PDCD4 , KBTBD7 , NOS3 , STRN , and Spry-1 . This review provides insights into the future advancement of safe miR-21 -based genetic therapy in the treatment of myocardial infarction.

Exploring the Relationship of Perivascular Adipose Tissue Inflammation and the Development of Vascular Pathologies.

Initially thought to only provide mechanical support for the underlying blood vessels, perivascular adipose tissue (PVAT) has now emerged as a regulator of vascular function. A healthy PVAT exerts anticontractile and anti-inflammatory actions on the underlying vasculature via the release of adipocytokines such as adiponectin, nitric oxide, and omentin. However, dysfunctional PVAT produces more proinflammatory adipocytokines such as leptin, resistin, interleukin- (IL-) 6, IL-1ß, and tumor necrosis factor-alpha, thus inducing an inflammatory response that contributes to the pathogenesis of vascular diseases. In this review, current knowledge on the role of PVAT inflammation in the development of vascular pathologies such as atherosclerosis and hypertension was discussed.

Kelulut Honey Regulates Sex Steroid Receptors in a Polycystic Ovary Syndrome Rat Model.

Reproductive and metabolic anomalies in polycystic ovary syndrome (PCOS) have been associated with the dysregulation of sex steroid receptors. Kelulut honey (KH) has been shown to be beneficial in PCOS-induced rats by regulating folliculogenesis and the oestrus cycle. However, no study has been conducted to evaluate KH's effect on sex steroid receptors in PCOS. Therefore, the current study examined the effects of KH, metformin, or clomiphene alone and in combination on the mRNA expression and protein distribution of androgen receptor (AR), oestrogen receptor α (ERα), oestrogen receptor ß (ERß), and progesterone receptor (PR) in PCOS-induced rats. The study used female Sprague-Dawley rats, which were treated orally with 1 mg/kg/day of letrozole for 21 days to develop PCOS. PCOS-induced rats were then divided and treated orally for 35 days with KH, metformin, clomiphene, KH + metformin, KH+ clomiphene and distilled water. In this study, we observed aberrant AR, ERα, ERß and PR expression in PCOS-induced rats compared with the normal control rats. The effects of KH treatment were comparable with clomiphene and metformin in normalizing the expression of AR, ERα, and ERß mRNA. However, KH, clomiphene and metformin did not affect PR mRNA expression and protein distribution. Hence, this study confirms the aberrant expression of sex steroid receptors in PCOS and demonstrates that KH treatment could normalise the sex steroid receptors profile. The findings provide a basis for future clinical trials to utilize KH as a regulator of sex steroid receptors in patients with PCOS.

Antioxidative and anti-inflammatory activities of Polygonum minus: a review of literature.

Inflammation and oxidative stress are involved in the pathogenesis of cardiovascular diseases such as atherosclerosis, hypertension and ischemic heart disease. Natural products play an important role as nutritional supplements with potential health benefits in cardiovascular diseases. Polygonum minus (PM) is an aromatic plant that is widely used as a flavoring agent in cooking and has been recognized as a plant with various medicinal properties including antioxidative and anti-inflammatory actions. Phytoconstituents found in PM such as phenolic and flavonoid compounds contribute to the plant's antioxidative and anti-inflammatory effects. We conducted this review to systematically identify articles related to the antioxidative and anti-inflammatory activities of PM. A computerized database search was conducted on Ovid MEDLINE, PubMed, Scopus, and ACS publication, from 1946 until May 2020, and the following keywords were used: 'Kesum OR Polygonum minus OR Persicaria minor' AND 'inflammat* OR oxida* OR antioxida*'. A total of 125 articles were obtained. Another eight additional articles were identified through Google Scholar and review articles. Altogether, 17 articles were used for data extraction, comprising 16 articles on antioxidant and one article on anti-inflammatory activity of PM. These studies consist of 14 in vitro studies, one in vivo animal study, one combined in vitro and in vivo study and one combined in vitro and ex vivo study. All the studies reported that PM exhibits antioxidative and anti-inflammatory activities which are most likely attributed to its high phenolic and flavonoid content.

The Association between Inflammation and Pulse Wave Velocity in Dyslipidemia: An Evidence-Based Review.

Dyslipidemia is associated with increased arterial stiffness (AS) which may lead to hypertension. Among the methods to assess AS are carotid-femoral and brachial-ankle pulse wave velocity. Dyslipidemia is also known to trigger inflammation. C-reactive protein (CRP) is one of the commonest inflammatory markers measured in the clinical setting. However, the association between inflammation and pulse wave velocity (PWV) in people with dyslipidemia is less studied. Therefore, this review investigated the association between inflammation (as measured by CRP) and PWV in dyslipidemia patients. The search of the literature was conducted via PubMed and Scopus database. The keywords used were "aortic stiffness" OR "arterial stiffness" OR "pulse wave velocity" OR "vascular stiffness" OR "carotid femoral pulse wave velocity" OR "pulse wave analysis" AND "inflammation" OR "c reactive protein" OR "c-reactive protein" OR "high sensitivity c reactive protein" AND "dyslipidemia" OR "hyperlipidemia" OR "hypercholesterolemia" OR "hyperlipoproteinemia" OR "hypertriglyceridemia". The following criteria were used: (1) only full-length original articles published in English language, (2) articles that reported the association between arterial stiffness measured as carotid-femoral PWV (cfPWV) or brachial-ankle PWV (baPWV) and CRP or high-sensitivity CRP, and (3) study involving human subjects. The search identified 957 articles published between 1980 and February 2020. Only eight articles fulfilled the inclusion criteria and were used for data extraction. Five of the studies were cross-sectional studies while another three studies were interventional studies. Seven out of eight papers found a significant positive association between AS and CRP, and the correlation ranged from mild to moderate association (Pearson r = 0.33 to r = 0.624). In conclusion, inflammation is associated with increased PWV in patients with dyslipidemia. This supports the involvement of inflammation in the development of AS in dyslipidemia.

Vascular Dysfunction among Malaysian Men with Increased BMI: An Indication of Synergistic Effect of Free Testosterone and Inflammation.

Background and objectives: Obesity is associated with poor vascular function and may lead to future cardiovascular disease (CVD). Obesity is also related to increased inflammation and a low testosterone level. This study was conducted to determine the relationship between inflammation, testosterone level, and vascular function among subjects with an increased body mass index (BMI) and to determine whether both low testosterone and high inflammation have synergistic effects towards vascular dysfunction. Materials and Methods: A total of 303 men aged 40-80 years were recruited from Klang Valley, Malaysia. Their height, weight, blood pressure (BP), lipid, blood glucose level, total testosterone (TT), free testosterone (FT), and C-reactive protein (CRP) were measured. The carotid femoral pulse wave velocity (PWVCF) and augmentation index (AI) were also recorded as markers of vascular function. Results: The mean age of all the subjects was 54.46 ± 9.77 years. Subjects were divided into a low/normal body mass index (BMI) group (BMI < 25 kg/m2; NG, n = 154) and high BMI group (BMI ≥ 25 kg/m2; OG, n = 149). The mean BMI for NG was 22.20 ± 1.94 kg/m2 while for OG was 28.87 ± 3.24 kg/m2 (p < 0.01). The level of TT (OG = 21.13 ± 6.44 versus NG = 16.18 ± 6.16 nmol/L, p < 0.01) and FT (OG = 0.34 ± 0.12 versus NG = 0.39 ± 0.11 nmol/L, p < 0.01) were reduced while the level of CRP [OG = 1.05 (2.80) versus NG = 0.50 (1.50) mmol/L, p = 0.01] was increased in OG compared to NG. PWVCF (OG = 8.55 ± 1.34 versus NG = 8.52 ± 1.42 m/s, p = 0.02) and AI (OG = 16.91% ± 6.00% versus 15.88% ± 5.58%, p < 0.01) were significantly increased in OG after adjustment for other CVD risk factors. The subjects that had both a low FT and an increased CRP had higher AI when compared to those with a high CRP and high FT (p < 0.01). Conclusions: The increased BMI was associated with vascular dysfunction, mediated by a low testosterone level and increased inflammation. Furthermore, having both conditions concurrently lead to higher vascular dysfunction. Weight loss, testosterone supplementation, and the anti-inflammatory agent may be beneficial for men to prevent vascular dysfunction.

Changes in IP3 Receptor Expression and Function in Aortic Smooth Muscle of Atherosclerotic Mice.

Peroxynitrite is an endothelium-independent vasodilator that induces relaxation via membrane hyperpolarization. The activation of IP3 receptors triggers the opening of potassium channels and hyperpolarization. Previously we found that relaxation to peroxynitrite was maintained during the development of atherosclerosis due to changes in the expression of calcium-regulatory proteins. In this study we investigated: (1) the mechanism of peroxynitrite-induced relaxation in the mouse aorta, (2) the effect of atherosclerosis on relaxation to peroxynitrite and other vasodilators, and (3) the effect of atherosclerosis on the expression and function of the IP3 receptor. Aortic function was studied using wire myography, and atherosclerosis was induced by fat-feeding ApoE-/- mice. The expression of IP3 receptors was studied using Western blotting and immunohistochemistry. Relaxation to peroxynitrite was attenuated by the IP3 antagonists 2-APB and xestospongin C and also the Kv channel blocker 4-aminopyridine (4-AP). Atherosclerosis attenuated vasodilation to cromakalim and the AMPK activator A769662 but not peroxynitrite. Relaxation was attenuated to a greater extent by 2-APB in atherosclerotic aortae despite the reduced expression of IP3 receptors. 4-AP was less effective in ApoE-/- mice fat-fed for 4 months. Peroxynitrite relaxation involves an IP3-induced calcium release and KV channel activation. This mechanism becomes less important as atherosclerosis develops, and relaxation to peroxynitrite may be maintained by increased calcium extrusion.

An investigation of the antiplatelet effects of succinobucol (AGI-1067).

Succinobucol is a phenolic antioxidant with anti-inflammatory and antiplatelet effects. Given the importance of oxidant stress in modulating platelet-platelet and platelet-vessel wall interactions, the aim of this study was to establish if antioxidant activity was responsible for the antiplatelet activity of succinobucol. Platelet aggregation in response to collagen and adenosine diphosphate (ADP) was studied in rabbit whole blood and platelet-rich plasma using impedance aggregometry. The effect of oxidant stress on aggregation, platelet lipid peroxides, and vascular tone was studied by incubating platelets, washed platelets or preconstricted rabbit iliac artery rings respectively with a combination of xanthine and xanthine oxidase (X/XO). To study the effect of succinobucol in vivo, anaesthetized rats were injected with up to 150 mg/kg succinobucol and aggregation measured in blood removed 15 mins later. Succinobucol (10-5-10-4 M) significantly attenuated platelet aggregation to collagen and ADP in whole blood and platelet-rich plasma. X/XO significantly increased aggregation to collagen and platelet lipid peroxides and this was reversed by succinobucol. Addition of X/XO to denuded rabbit iliac arteries caused a dose-dependent relaxation which was significantly inhibited by succinobucol. In vivo administration up to 150 mg/kg had no effect on heart rate or mean arterial blood pressure but significantly inhibited platelet aggregation to collagen ex vivo. In conclusion, succinobucol displays anti-platelet activity in rabbit and rat blood and reverses the increase in platelet aggregation in response to oxidant stress.

Role of rutin on nitric oxide synthesis in human umbilical vein endothelial cells.

Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is a major antiatherogenic factor in the blood vessel. Oxidative stress plays an important role in the pathogenesis of various cardiovascular diseases, including atherosclerosis. Decreased availability of endothelial NO promotes the progression of endothelial dysfunction and atherosclerosis. Rutin is a flavonoid with multiple cardiovascular protective effects. This study aimed to investigate the effects of rutin on eNOS and NO production in cultured human umbilical vein endothelial cells (HUVEC). HUVEC were divided into four groups: control; oxidative stress induction with 180 µM H2O2; treatment with 300 µM rutin; and concomitant induction with rutin and H2O2 for 24 hours. HUVEC treated with rutin produced higher amount of NO compared to control (P < 0.01). In the oxidative stress-induced HUVEC, rutin successfully induced cells' NO production (P < 0.01). Rutin promoted NO production in HUVEC by inducing eNOS gene expression (P < 0.05), eNOS protein synthesis (P < 0.01), and eNOS activity (P < 0.05). Treatment with rutin also led to increased gene and protein expression of basic fibroblast growth factor (bFGF) in HUVEC. Therefore, upregulation of eNOS expression by rutin may be mediated by bFGF. The results showed that rutin may improve endothelial function by augmenting NO production in human endothelial cells.

Unraveling the path to osteoarthritis management: targeting chondrocyte apoptosis for therapeutic intervention.

Osteoarthritis (OA) is a chronic disease affecting joints and further causing disabilities. This disease affects around 240 million people worldwide. It is a multifactorial disease, and its etiology is difficult to determine. Although numerous therapeutic strategies are available, the therapies are aimed at reducing pain and improving patients' quality of life. Hence, there is an urgent need to develop disease-modifying drugs (DMOAD) that can reverse or halt OA progression. Apoptosis is a cell removal process that is important in maintaining homeostatic mechanisms in the development and sustaining cell population. The apoptosis of chondrocytes is believed to play an important role in OA progression due to poor chondrocytes self-repair abilities to maintain the extracellular matrix (ECM). Hence, targeting chondrocyte apoptosis can be one of the potential therapeutic strategies in OA management. There are various mediators and targets available to inhibit apoptosis such as autophagy, endoplasmic reticulum (ER) stress, oxidative stress, and inflammation. As such, this review highlights the importance and potential targets that can be aimed to reduce chondrocyte apoptosis.

Resistance Training in Cardiovascular Diseases: A Review on Its Effectiveness in Controlling Risk Factors.

Cardiovascular Disease (CVD), a term encompassing various disorders affecting the heart and blood vessels, includes coronary artery disease (CAD). CAD is primarily due to the development of atherosclerotic plaques that disrupt blood flow, oxygenation, and nutrient delivery to the myocardium. Risk factors contributing to CAD progression include smoking, hypertension, diabetes mellitus (DM), dyslipidaemia, and obesity. While aerobic exercise (AE) has shown promising results in controlling CVD risk factors, the impact of resistance training (RT) has not been extensively investigated. This review aims to describe the effects of RT on CVD risk factors based on studies retrieved from PubMed and Google Scholar databases. Both isometric and isotonic RT have been found to decrease systolic blood pressure (SBP), diastolic blood pressure, or mean arterial pressure, with SBP showing a more significant reduction. Hypertensive patients engaging in RT alongside a calorie-restricted diet demonstrated significant improvements in blood pressure. RT is associated with increased nitric oxide bioavailability, sympathetic modulation, and enhanced endothelial function. In type-2 DM patients, 8-12 weeks of RT led to improvements in fasting blood glucose levels, insulin secretion, metabolic syndrome risk, and glucose transporter numbers. Combining AE with RT had a more significant impact in reducing insulin resistance and enhancing blood glucose compared to performing exercises separately. It also significantly decreased total cholesterol, triglycerides, and low-density lipoprotein levels while increasing high-density lipoprotein within 12 weeks of application. However, improvements are considered insignificant when lipid levels are already low to normal at baseline. The administration of RT resulted in weight loss and improved body mass index, with more pronounced effects seen when combining AE with RT and a calorie-restricted diet. Considering these results, the administration of RT, either alone or in combination with AE, proves beneficial in rehabilitating CAD patients by improving various risk factors.