A Comprehensive Analysis into the Therapeutic Application of Natural Products as SIRT6 Modulators in Alzheimer's Disease, Aging, Cancer, Inflammation, and Diabetes.

Natural products have long been used as drugs to treat a wide array of human diseases. The lead compounds discovered from natural sources are used as novel templates for developing more potent and safer drugs. Natural products produce biological activity by binding with biological macromolecules, since natural products complement the protein-binding sites and natural product-protein interactions are already optimized in nature. Sirtuin 6 (SIRT6) is an NAD+ dependent histone deacetylase enzyme and a unique Sirtuin family member. It plays a crucial role in different molecular pathways linked to DNA repair, tumorigenesis, glycolysis, gluconeogenesis, neurodegeneration, cardiac hypertrophic responses, etc. Thus, it has emerged as an exciting target of several diseases such as cancer, neurodegenerative diseases, aging, diabetes, metabolic disorder, and heart disease. Recent studies have shown that natural compounds can act as modulators of SIRT6. In the current review, a list of natural products, their sources, and their mechanisms of SIRT6 activity modulation has been compiled. The potential application of these naturally occurring SIRT6 modulators in the amelioration of major human diseases such as Alzheimer's disease, aging, diabetes, inflammation, and cancer has also been delineated. Natural products such as isoquercetin, luteolin, and cyanidin act as SIRT6 activators, whereas vitexin, catechin, scutellarin, fucoidan, etc. work as SIRT6 inhibitors. It is noteworthy to mention that quercetin acts as both SIRT6 activator and inhibitor depending on its concentration used. Although none of them were found as highly selective and potent modulators of SIRT6, they could serve as the starting point for developing selective and highly potent scaffolds for SIRT6.

In Vivo Anti-diarrheal Activity of Methanolic Extract of Streblus asper Leaves Stimulating the Na+/K+-ATPase in Swiss Albino Rats.

Streblus asper Lour., traditionally used for anti-diarrheal effects as like dysentery and diarrhea. The present study aims to prove the anti-diarrheal activities of methanolic extract of leaves of S. asper in animal models. The anti-diarrheal activity was evaluated using castor oil-induced diarrhea and magnesium sulphate-induced diarrhea models whereas anti-motility activities were investigated using gastrointestinal transit test examined in animal models. In castor oil-induced diarrhea model, methanolic extract of S. asper (MESA) at the doses of 100, 200, and 400 mg/kg produced statistically significant (P < 0.001) decreased the number of diarrheal feces of rats against castor oil-induced diarrhea as well as magnesium sulphate-induced diarrhea model also showed the same manner. In gastrointestinal transit test, delayed gastric emptying time decreased significantly (P < 0.001), the propulsion of charcoal meal in the gastrointestinal tract which also showed a dose-dependent manner in rats. The recent study indicates that MESA possesses anti-diarrheal property. The findings represent a rational explanation for its use in traditional medicine for the management of diarrhea management.

Inducible transgene expression in CHO cells using an artificial transcriptional activator with estrogen-binding domain.

Biopharmaceuticals, including therapeutic antibodies, are rapidly growing products in the pharmaceutical market. Mammalian cells, such as Chinese hamster ovary (CHO) cells, are widely used as production hosts because recombinant antibodies require complex three-dimensional structures modified with sugar chains. Recombinant protein production using mammalian cells is generally performed with cell growth. In this study, we developed a technology that controls cell growth and recombinant protein production to induce recombinant protein production with predetermined timing. Expression of green fluorescent protein (GFP) gene and a single-chain antibody fused with the Fc-region of the human IgG1 (scFv-Fc) gene can be induced and mediated by the estrogen receptor-based artificial transcription factor Gal4-ERT2-VP16 and corresponding inducer drugs. We generated CHO cells using an artificial gene expression system. The addition of various concentrations of inducer drugs to the culture medium allowed control of proliferation and transgene expression of the engineered CHO cells. Use of 4-hydroxytamoxifen, an antagonist of estrogen, as an inducing agent yielded high gene expression at a concentration more than 10-fold lower than that of ß-estradiol. When scFv-Fc was produced under inducing conditions, continuous production was possible for more than 2 weeks while maintaining high specific productivity (57 pg cell-1 day-1 ). This artificial gene expression control system that utilizes the estrogen response of estrogen receptors can be an effective method for inducible production of biopharmaceuticals.

The Neuropathological Impacts of COVID-19: Challenges and Alternative Treatment Options for Alzheimer's Like Brain Changes on Severely SARS-CoV-2 Infected Patients.

Recently, some researchers claimed neuropathological changes lead to Alzheimer's-like brains after severe infection of SARS-CoV-2. Several mechanisms have been postulated on how SARS-CoV-2 neurological damage leads to Alzheimer's disease (AD) development. Neurobiochemical changes during infection may significantly induce Alzheimer's disease in severely COVID-19 infected people. The immune system is also compromised while infected by this novel coronavirus. However, recent studies are insufficient to conclude the relationship between Alzheimer's disease and COVID-19. This review demonstrates the possible pathways of neuropathological changes induced by the SARS-CoV-2 virus in AD patients or leading to AD in COVID-19 patients. Therefore, this study delineates the challenges for COVID-19 infected AD patients and the mechanism of actions of natural compounds and alternative treatments to overcome those. Furthermore, animal studies and a large cohort of COVID-19 survivors who showed neuroinflammation and neurological changes may augment the research to discover the relationship between Alzheimer's disease and COVID-19.

Plausibility of natural immunomodulators in the treatment of COVID-19-A comprehensive analysis and future recommendations.

The COVID-19 pandemic has inflicted millions of deaths worldwide. Despite the availability of several vaccines and some special drugs approved for emergency use to prevent or treat this disease still, there is a huge concern regarding their effectiveness, adverse effects, and most importantly, their efficacy against the new variants. A cascade of immune-inflammatory responses is involved with the pathogenesis and severe complications with COVID-19. People with dysfunctional and compromised immune systems display severe complications, including acute respiratory distress syndrome, sepsis, multiple organ failure etc., when they get infected with the SARS-CoV-2 virus. Plant-derived natural immune-suppressant compounds, such as resveratrol, quercetin, curcumin, berberine, luteolin, etc., have been reported to inhibit pro-inflammatory cytokines and chemokines. Therefore, natural products with immunomodulatory and anti-inflammatory potential could be plausible targets to treat this contagious disease. This review aims to delineate the clinical trials status and outcomes of natural compounds with immunomodulatory potential in COVID-19 patients along with the outcomes of their in-vivo studies. In clinical trials several natural immunomodulators resulted in significant improvement of COVID-19 patients by diminishing COVID-19 symptoms such as fever, cough, sore throat, and breathlessness. Most importantly, they reduced the duration of hospitalization and the need for supplemental oxygen therapy, improved clinical outcomes in patients with COVID-19, especially weakness, and eliminated acute lung injury and acute respiratory distress syndrome. This paper also discusses many potent natural immunomodulators yet to undergo clinical trials. In-vivo studies with natural immunomodulators demonstrated reduction of a wide range of proinflammatory cytokines. Natural immunomodulators that were found effective, safe, and well tolerated in small-scale clinical trials are warranted to undergo large-scale trials to be used as drugs to treat COVID-19 infections. Alongside, compounds yet to test clinically must undergo clinical trials to find their effectiveness and safety in the treatment of COVID-19 patients.

A comprehensive look into the association of vitamin D levels and vitamin D receptor gene polymorphism with obesity in children.

Childhood obesity accounts for several psychosocial and clinical consequences. Psychosocial consequences include lower self-esteem, social isolation, poor academic achievement, peer problems, and depression, whereas clinical consequences are cardiovascular diseases, type 2 diabetes, dyslipidemia, cancer, autoimmune diseases, girls early polycystic ovarian syndrome (PCOS), asthma, bone deformities, etc. A growing number of studies have uncovered the association of childhood obesity and its consequences with vitamin-D (vit-D) deficiency and vitamin-D receptor (VDR) gene polymorphisms such as single nucleotide polymorphisms (SNPs), e.g., TaqI, BsmI, ApaI, FokI, and Cdx2. Considering the impact of vit-D deficiency and VDR gene polymorphisms, identifying associated factors and risk groups linked to lower serum vit-D levels and prevention of obesity-related syndromes in children is of utmost importance. Previously published review articles mainly focused on the association of vit-D deficiency with obesity or other non-communicable diseases in children. The nature of the correlation between vit-D deficiency and VDR gene polymorphisms with obesity in children is yet to be clarified. Therefore, this review attempts to delineate the association of obesity with these two factors by identifying the molecular mechanism of the relationship.

CRISPR-Based Programmable Nucleic Acid-Binding Protein Technology Can Specifically Detect Fatal Tropical Disease-Causing Pathogens.

Diagnostic approaches capable of ultrasensitive pathogen detection from low-volume clinical samples, running without any sophisticated instrument and laboratory setup, are easily field-deployable, inexpensive, and rapid, and are considered ideal for monitoring disease progression and surveillance. However, standard pathogen detection methods, including culture and microscopic observation, antibody-based serologic tests, and primarily polymerase chain reaction (PCR)-oriented nucleic acid screening techniques, have shortcomings that limit their widespread use in responding to outbreaks and regular diagnosis, especially in remote resource-limited settings (RLSs). Recently, clustered regularly interspaced short palindromic repeats (CRISPR)-based programmable technology has emerged to challenge the unmet criteria of conventional methods. It consists of CRISPR-associated proteins (Cas) capable of targeting virtually any specific RNA or DNA genome based on the guide RNA (gRNA) sequence. Furthermore, the discovery of programmable trans-cleavage Cas proteins like Cas12a and Cas13 that can collaterally damage reporter-containing single-stranded DNA or RNA upon formation of target Cas-gRNA complex has strengthened this technology with enhanced sensitivity. Current advances, including automated multiplexing, ultrasensitive single nucleotide polymorphism (SNP)-based screening, inexpensive paper-based lateral flow readouts, and ease of use in remote global settings, have attracted the scientific community to introduce this technology in nucleic acid-based precise detection of bacterial and viral pathogens at the point of care (POC). This review highlights CRISPR-Cas-based molecular technologies in diagnosing several tropical diseases, namely malaria, zika, chikungunya, human immunodeficiency virus and acquired immunodeficiency syndrome (HIV-AIDS), tuberculosis (TB), and rabies.

CRISPR is a useful biological tool for detecting nucleic acid of SARS-CoV-2 in human clinical samples.

The recent pandemic of novel coronavirus disease (COVID-19) has spread globally and infected millions of people. The quick and specific detection of the nucleic acid of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) remains a challenge within healthcare providers. Currently, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) is the widely used method to detect the SARS-CoV-2 from the human clinical samples. RT-qPCR is expensive equipment and needs skilled personnel as well as lengthy detection time. RT-qPCR limitation needed an alternative healthcare technique to overcome with a fast and cheaper detection method. By applying the principles of CRISPR technology, several promising detection methods giving hope to the healthcare community. CRISPR-based detection methods include SHERLOCK-Covid, STOP-Covid, AIOD-CRISPR, and DETECTR platform. These methods have comparative advantages and drawbacks. Among these methods, AIOD-CRISPR and DETECTR are reasonably better diagnostic methods than the others if we compare the time taken for the test, the cost associated with each test, and their capability of detecting SARS-CoV-2 in the clinical samples. It may expect that the promising CRISPR-based methods would facilitate point-of-care (POC) applications in the CRISPR-built next-generation novel coronavirus diagnostics.

Overview and Current Status of Alzheimer's Disease in Bangladesh.

Alzheimer's disease (AD) is a complex neurological disorder with economic, social, and medical burdens which is acknowledged as leading cause of dementia marked by the accumulation and aggregation of amyloid-ß peptide and phosphorylated tau (p-tau) protein and concomitant dementia, neuron loss and brain atrophy. AD is the most prevalent neurodegenerative brain disorder with sporadic etiology, except for a small fraction of cases with familial inheritance where familial forms of AD are correlated to mutations in three functionally related genes: the amyloid-ß protein precursor and presenilins 1 and 2, two key γ-secretase components. The common clinical features of AD are memory impairment that interrupts daily life, difficulty in accomplishing usual tasks, confusion with time or place, trouble understanding visual images and spatial relationships. Age is the most significant risk factor for AD, whereas other risk factors correlated with AD are hypercholesterolemia, hypertension, atherosclerosis, coronary heart disease, smoking, obesity, and diabetes. Despite decades of research, there is no satisfying therapy which will terminate the advancement of AD by acting on the origin of the disease process, whereas currently available therapeutics only provide symptomatic relief but fail to attain a definite cure and prevention. This review also represents the current status of AD in Bangladesh.