Heavy Metal Exposure-Induced Cardiovascular Diseases: Molecular Mechanisms and Therapeutic Role of Antioxidants.

Globally, cardiovascular diseases (CVDs) are the main cause of mortality every year worldwide. CVD health is influenced by various health factors, such as blood pressure, cholesterol levels, and glucose control. The main risk factors include smoking, physical activity, food intake, and body mass index. Around 90% of CVDs could be prevented by controlling these risk factors. Heavy metals are indigenous to the environment of the earth. However, modern lifestyles have led to the exploitation of our environment by unconstrained use of heavy metals. Though heavy metals are essential components, they are hazardous to humans and living systems due to their persistent and non-degradable nature. The mainpurpose of this study is to provide a literature review on the mechanisms of heavy metals, particularly arsenic, lead, and cadmium, that cause cardiovascular diseases. The major mechanism by which heavy metals result in various modalities of cardiovascular disease is the generation of reactive species and the depletionof the antioxidant reserves inside the biological system. The generation of reactive species gradually leads to the activation of various signaling pathways, resulting in either apoptosis or unrestricted cell growth. These unfavorable conditions result in a state when there is an imbalance between reactive species generation and antioxidant activity. Both endogenously present antioxidants and dietary antioxidants are very much essential in regulating the redox potential of the body. They help in the detoxification and excretion of heavy metals and their metabolites in the biological system. Therefore, recognizing the role of heavy metals in cardiovascular health is crucial for developing preventive strategies and interventions aimed at mitigating their adverse effects on human health.

The effect of post-mortem computed tomography angiography (PMCTA) on biomarkers of coronary artery disease.

Coronary atherosclerosis is due to build-up of plaque within the coronary arteries. Post-mortem computed tomography (PMCT) allows non or minimally invasive visualization of abnormalities prior to an autopsy, however PMCT-angiography (PMCTA) greatly enhances relevant findings, especially in viewing the cardiovascular system which is important in the diagnosis of coronary atherosclerosis. Contrast media used in PMCTA however has been reported to cause distortion of tissue which may interfere with post-mortem investigation outcomes. A cross sectional study to investigate the effect of PMCTA on tissue biomarkers in coronary arteries was performed involving cases brought in dead to the Institute and Accident and Emergency Unit. Sixty-three autopsy cases were included in this study, whereby 18 cases underwent PMCT while 45 cases underwent PMCTA. The subjects subsequently had a conventional autopsy where coronary artery sections were collected for standard histological examination and immunohistochemistry examination for endothelial inflammatory (CD36), prothrombogenic (TPA) and plaque stability (MMP-9) markers. The subjects consisted of 55 males and 8 females with a mean age ±SD of 49 ± 18.11 years. There were no significant differences in the coronary artery endothelial expression of CD36, MMP-9 and TPA between PMCT and PMCTA subjects. PMCTA does not alter CD36, TPA and MMP-9 markers supporting the safe use of PMCTA in post-mortem examinations.

Chemical Constituents and Biological Activities of Piper as Anticancer Agents: A Review.

Cancer has become the primary cause of death worldwide, and anticancer drugs are used to combat this disease. Synthesis of anticancer drugs has limited success due to adverse side effects has made compounds from natural products with minimal toxicity gain much popularity. Piper species are known to have a biological effect on human health. The biological activity is due to Piper species rich with active secondary metabolites that can combat most diseases, including cancer. This review will discuss the phytochemistry of Piper species and their anticancer activity. The identification and characterization of ten active metabolites isolated from Piper species were discussed in detail and their anticancer mechanism. These metabolites were mainly found could inhibit anticancer through caspase and P38/JNK pathways. The findings discussed in this review support the therapeutic potential of Piper species against cancer due to their rich source of active metabolites with demonstrated anticancer activity.

Natural Products Targeting PI3K/AKT in Myocardial Ischemic Reperfusion Injury: A Scoping Review.

This scoping review aimed to summarize the effects of natural products targeting phosphoinositide-3-kinases/serine/threonine kinase (PI3K/AKT) in myocardial ischemia-reperfusion injury (MIRI). The review details various types of natural compounds such as gypenoside (GP), gypenoside XVII (GP-17), geniposide, berberine, dihydroquercetin (DHQ), and tilianin which identified to reduce MIRI in vitro and in vivo by regulating the PI3K/AKT signaling pathway. In this study, 14 research publications that met the inclusion criteria and exclusion criteria were shortlisted. Following the intervention, we discovered that natural products effectively improved cardiac functions through regulation of antioxidant status, down-regulation of Bax, and up-regulation of Bcl-2 and caspases cleavage. Furthermore, although comparing outcomes can be challenging due to the heterogeneity in the study model, the results we assembled here were consistent, giving us confidence in the intervention's efficacy. We also discussed if MIRI is associated with multiple pathological condition such as oxidative stress, ERS, mitochondrial injury, inflammation, and apoptosis. This brief review provides evidence to support the huge potential of natural products used in the treatment of MIRI due to their various biological activities and drug-like properties.

Natural Bioactive Compounds Targeting NADPH Oxidase Pathway in Cardiovascular Diseases.

Cardiovascular disease (CVD) is the leading cause of death worldwide, in both developed and developing countries. According to the WHO report, the morbidity and mortality caused by CVD will continue to rise with the estimation of death going up to 22.2 million in 2030. NADPH oxidase (NOX)-derived reactive oxygen species (ROS) production induces endothelial nitric oxide synthase (eNOS) uncoupling and mitochondrial dysfunction, resulting in sustained oxidative stress and the development of cardiovascular diseases. Seven distinct members of the family have been identified of which four (namely, NOX1, 2, 4 and 5) may have cardiovascular functions. Currently, the treatment and management plan for patients with CVDs mainly depends on the drugs. However, prolonged use of prescribed drugs may cause adverse drug reactions. Therefore, it is crucial to find alternative treatment options with lesser adverse effects. Natural products have been gaining interest as complementary therapy for CVDs over the past decade due to their wide range of medicinal properties, including antioxidants. These might be due to their potent active ingredients, such as flavonoid and phenolic compounds. Numerous natural compounds have been demonstrated to have advantageous effects on cardiovascular disease via NADPH cascade. This review highlights the potential of natural products targeting NOX-derived ROS generation in treating CVDs. Emphasis is put on the activation of the oxidases, including upstream or downstream signalling events.

Incorporating Insulin Growth Factor-1 into Regenerative and Personalized Medicine for Cardiovascular Disease: A Systematic Review.

BACKGROUND: Cardiovascular disease (CVD) is one of the world's leading causes of increased morbidity and mortality. Current interventions for CVD, including percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG), carry certain risks and complications, which may also affect the patient's quality of life. It is important to minimize those risks and complications while speeding up the recovery. Insulin Growth Factor-1 (IGF-1) is a growth factor responsible for cellular migration, proliferation, differentiation, and angiogenesis, which supports cardiovascular regeneration. METHODS: In light of the current trend of regenerative medicine, the present review aims to pool data relating to the incorporation of IGF-1 in regenerative medicine and provide input on the current research gaps and concerns arising on translating this approach from benchwork into clinical settings. RESULTS: Using the keywords IGF-1 'OR' Insulin Growth Factor 1 'AND' Mesenchymal Stem Cells 'AND' Tissue Healing from 2009 to 2020, we identified 160 and 52 from Medline and PubMed, screening out 202 articles due to non-fulfilment of the inclusion criteria. CONCLUSION: Incorporating IGF-1 into regenerative and personalized medicine may be promising for treating CVD; however, the concerns include the role of IGF-1 in inducing cancer growth and its ability to migrate to the specific site of injury, especially for those who present with multiple pathologies should be addressed prior to its translation from bench work into clinical settings.

Age estimation from mandibles in Malay: A 2D geometric morphometric analysis.

Objectives: In this study, the sizes and forms of mandibles in various age groups of the Malay population were measured and compared. Methods: Geometric morphometric (GM) analysis of mandibles from 400 dental panoramic tomography (DPT) specimens was conducted. The MorphoJ program was used to perform generalized Procrustes analysis (GPA), Procrustes ANOVA, principal component analysis (PCA), discriminant function analysis (DFA), and canonical variate analysis (CVA). In the tpsDig2 program, the 27 landmarks were applied to the DPT radiographs. Variations in mandibular size and form were categorized into four age groups: group 1 (15-24 years), group 2 (25-34 years), group 3 (35-44 years), and group 4 (45-54 years). Results: The diversity in mandibular shape among the first eight principal components was 81%. Procrustes ANOVA revealed significant shape differences (P < 0.001) among age groups. Mahalanobis distances indicated substantial differences among all age groups; group 1 and group 4 scored highest, at 2.114. The ranges for the cross-validation and discriminant function tests were 90-72% and 81-49%, respectively. Conclusion: GM analysis through radiography is a simple, non-invasive, and non-destructive method of estimating age by using the mandible. GM analysis is unique because it can visualize the changes in mandible shape among age groups. This method should aid in age identification in forensic odontology investigations.

Distribution of frontal sinus pattern amongst Malaysian population: a skull radiograph study.

Frontal sinus has unique anatomical features that are distinct to every population. However, the distribution of frontal sinus patterns has yet to be explored in the Malaysian population. This study aimed to describe the distribution of frontal sinus patterns among adult Malaysians. 409 adult Malaysian posteroanterior skull radiographs, consisting of 200 males and 209 females of Malay, Chinese, and Indian races aged between 20-69 years old, were included in the study. The frontal sinus patterns were classified according to total and percentage of presence or absence of frontal sinus, symmetry or asymmetrical (right or left dominant), unilateral absence (right or left), bilateral absence, and lobulation. The findings showed that bilateral presence of frontal sinus is common, in 95.4% of individuals and bilateral absence was noted in 2.7% individuals. Unilateral absence was found in 2.0% of individuals. Asymmetrical frontal sinus was observed in 54.5% of population meanwhile 40.8% showed symmetrical frontal sinus. The majority of individuals, regardless of sex, race, and age, possessed 1 to 3 lobes on both sides of the frontal sinus. The findings suggest that the frontal sinus is highly asymmetric, and the absence of the frontal sinus is rare. This morphological variation provides an insight into the landmarking placement for measurement during forensic application and assists neurosurgeons in surgical procedure to avoid breaching of the frontal sinus.

Matrix Metalloproteinases in Chemoresistance: Regulatory Roles, Molecular Interactions, and Potential Inhibitors.

Cancer is one of the major causes of death worldwide. Its treatments usually fail when the tumor has become malignant and metastasized. Metastasis is a key source of cancer recurrence, which often leads to resistance towards chemotherapeutic agents. Hence, most cancer-related deaths are linked to the occurrence of chemoresistance. Although chemoresistance can emerge through a multitude of mechanisms, chemoresistance and metastasis share a similar pathway, which is an epithelial-to-mesenchymal transition (EMT). Matrix metalloproteinases (MMPs), a class of zinc and calcium-chelated enzymes, are found to be key players in driving cancer migration and metastasis through EMT induction. The aim of this review is to discuss the regulatory roles and associated molecular mechanisms of specific MMPs in regulating chemoresistance, particularly EMT initiation and resistance to apoptosis. A brief presentation on their potential diagnostic and prognostic values was also deciphered. It also aimed to describe existing MMP inhibitors and the potential of utilizing other strategies to inhibit MMPs to reduce chemoresistance, such as upstream inhibition of MMP expressions and MMP-responsive nanomaterials to deliver drugs as well as epigenetic regulations. Hence, manipulation of MMP expression can be a powerful tool to aid in treating patients with chemo-resistant cancers. However, much still needs to be done to bring the solution from bench to bedside.

Natural Product-based Nanomedicine: Recent Advances and Issues for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) affects the elderly and is characterized by progressive neurodegeneration caused by different pathologies. The most significant challenges in treating AD include the inability of medications to reach the brain because of its poor solubility, low bioavailability, and the presence of the blood-brain barrier (BBB). Additionally, current evidence suggests the disruption of BBB plays an important role in the pathogenesis of AD. One of the critical challenges in treating AD is the ineffective treatments and their severe adverse effects. Nanotechnology offers an alternative approach to facilitate the treatment of AD by overcoming the challenges in drug transport across the BBB. Various nanoparticles (NP) loaded with natural products were reported to aid in drug delivery for the treatment of AD. The nano-sized entities of NP are great platforms for incorporating active materials from natural products into formulations that can be delivered effectively to the intended action site without compromising the material's bioactivity. The review highlights the applications of medicinal plants, their derived components, and various nanomedicinebased approaches for the treatment of AD. The combination of medicinal plants and nanotechnology may lead to new theragnostic solutions for the treatment of AD in the future.

Biological Activities of Paeonol in Cardiovascular Diseases: A Review.

Paeonol is a naturally existing bioactive compound found in the root bark of Paeonia suffruticosa and it is traditionally used in Chinese medicine for the prevention and management of cardiovascular diseases. To date, a great deal of studies has been reported on the pharmacological effects of paeonol and its mechanisms of action in various diseases and conditions. In this review, the underlying mechanism of action of paeonol in cardiovascular disease has been elucidated. Recent studies have revealed that paeonol treatment improved endothelium injury, demoted inflammation, ameliorated oxidative stress, suppressed vascular smooth muscle cell proliferation, and repressed platelet activation. Paeonol has been reported to effectively protect the cardiovascular system either employed alone or in combination with other traditional medicines, thus, signifying it could be a hypothetically alternative or complementary atherosclerosis treatment. This review summarizes the biological and pharmacological activities of paeonol in the treatment of cardiovascular diseases and its associated underlying mechanisms for a better insight for future clinical practices.

Geometric morphometric analysis of malocclusion on lateral cephalograms in Malaysian population.

Geometric morphometrics is a new approach for shape identification in diagnosis of malocclusion. Lateral cephalogram is an X-ray that taken for diagnosing malocclusion in dental setting. The aim of this study was to determine the differences of craniofacial shape in malocclusion by application of two-dimensional geometric morphometrics and to compile the database of malocclusion in adult Malaysian population. Lateral cephalogram radiographs of 381 adults Malaysia (age 18-45) were retrieved retrospectively and assigned to three groups according to their occlusion: class I, class II, and class III. The geometric morphometric shape study incorporated nine landmarks and was analyzed in details using tpsUtil p software. Geometric morphometric analysis such was done using MorphoJ software. The results of the principal component's analysis (PCA) yielded 14 main components responsible for 100% of the variation exhibited by the malocclusion with three highly significant PCA. The highest Mahalanobis distances were exhibited by the malocclusion class II and III population. The Procrustes ANOVA showed that the shape effect was highly significant (P<0.01). The discriminant function analysis showed the high percentage of 80% discriminate among the malocclusions after cross-validation. There are significant differences for ANB angle (A point-Nasion-B point) in all malocclusion groups. Class II has the widest ANB angle while class III has the most acute ANB angle. Skeletal shape was clearly associated with dental malocclusion and showed considerable variation. Geometric morphometrics is an alternative research tool and can be used for diagnosing individual classification of malocclusion.