Evaluate the in vitro effect of anthracycline and alkylating cytophosphane chemotherapeutics on dopaminergic neurons.

BACKGROUND: Iatrogenesis is an inevitable global threat to healthcare that drastically increases morbidity and mortality. Cancer is a fatal pathological condition that affects people of different ages, sexes, and races around the world. In addition to the detrimental cancer pathology, one of the most common contraindications and challenges observed in cancer patients is severe adverse drug effects and hypersensitivity reactions induced by chemotherapy. Chemotherapy-induced cognitive neurotoxicity is clinically referred to as Chemotherapy-induced cognitive impairment (CICI), chemobrain, or chemofog. In addition to CICI, chemotherapy also causes neuropsychiatric issues, mental disorders, hyperarousal states, and movement disorders. A synergistic chemotherapy regimen of Doxorubicin (Anthracycline-DOX) and Cyclophosphamide (Alkylating Cytophosphane-CPS) is indicated for the management of various cancers (breast cancer, lymphoma, and leukemia). Nevertheless, there are limited research studies on Doxorubicin and Cyclophosphamide's pharmacodynamic and toxicological effects on dopaminergic neuronal function. AIM: This study evaluated the dopaminergic neurotoxic effects of Doxorubicin and Cyclophosphamide. METHODS AND RESULTS: Doxorubicin and Cyclophosphamide were incubated with dopaminergic (N27) neurons. Neuronal viability was assessed using an MTT assay. The effect of Doxorubicin and Cyclophosphamide on various prooxidants, antioxidants, mitochondrial Complex-I & IV activities, and BAX expression were evaluated by Spectroscopic, Fluorometric, and RT-PCR methods, respectively. Prism-V software (La Jolla, CA, USA) was used for statistical analysis. Chemotherapeutics dose-dependently inhibited the proliferation of the dopaminergic neurons. The dopaminergic neurotoxic mechanism of Doxorubicin and Cyclophosphamide was attributed to a significant increase in prooxidants, a decrease in antioxidants, and augmented apoptosis without affecting mitochondrial function. CONCLUSION: This is one of the first reports that reveal Doxorubicin and Cyclophosphamide induce significant dopaminergic neurotoxicity. Thus, Chemotherapy-induced adverse drug reaction issues substantially persist during and after treatment and sometimes never be completely resolved clinically. Consequently, failure to adopt adequate patient care measures for cancer patients treated with certain chemotherapeutics might substantially raise the incidence of numerous movement disorders.

Opening avenues for treatment of neurodegenerative disease using post-biotics: Breakthroughs and bottlenecks in clinical translation.

Recent studies have indicated the significant involvement of the gut microbiome in both human physiology and pathology. Additionally, therapeutic interventions based on microbiome approaches have been employed to enhance overall health and address various diseases including aging and neurodegenerative disease (ND). Researchers have explored potential links between these areas, investigating the potential pathogenic or therapeutic effects of intestinal microbiota in diseases. This article provides a summary of established interactions between the gut microbiome and ND. Post-biotic is believed to mediate its neuroprotection by elevating the level of dopamine and reducing the level of α-synuclein in substantia nigra, protecting the loss of dopaminergic neurons, reducing the aggregation of NFT, reducing the deposition of amyloid ß peptide plagues and ameliorating motor deficits. Moreover, mediates its neuroprotective activity by inhibiting the inflammatory response (decreasing the expression of TNFα, iNOS expression, free radical formation, overexpression of HIF-1α), apoptosis (i.e. active caspase-3, TNF-α, maintains the level of Bax/Bcl-2 ratio) and promoting BDNF secretion. It is also reported to have good antioxidant activity. This review offers an overview of the latest findings from both preclinical and clinical trials concerning the use of post-biotics in ND.

The Influence of Kynurenine Metabolites on Neurodegenerative Pathologies.

As the kynurenine pathway's links to inflammation, the immune system, and neurological disorders became more apparent, it attracted more and more attention. It is the main pathway through which the liver breaks down Tryptophan and the initial step in the creation of nicotinamide adenine dinucleotide (NAD+) in mammals. Immune system activation and the buildup of potentially neurotoxic substances can result from the dysregulation or overactivation of this pathway. Therefore, it is not shocking that kynurenines have been linked to neurological conditions (Depression, Parkinson's, Alzheimer's, Huntington's Disease, Schizophrenia, and cognitive deficits) in relation to inflammation. Nevertheless, preclinical research has demonstrated that kynurenines are essential components of the behavioral analogs of depression and schizophrenia-like cognitive deficits in addition to mediators associated with neurological pathologies due to their neuromodulatory qualities. Neurodegenerative diseases have been extensively associated with neuroactive metabolites of the kynurenine pathway (KP) of tryptophan breakdown. In addition to being a necessary amino acid for protein synthesis, Tryptophan is also transformed into the important neurotransmitters tryptamine and serotonin in higher eukaryotes. In this article, a summary of the KP, its function in neurodegeneration, and the approaches being used currently to target the route therapeutically are discussed.

Harnessing the neuroprotective effect of oral administration of benfotiamine in MPTP induced Parkinson's disease in rats.

The study was performed to evaluate the neuroprotective effects of Benfotiamine (BFT) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) in rats. The rats were given daily doses of BFT (100 mg/kg, 200 mg/kg) through oral administration for 42 days. The rats were given a single bilateral dosage of MPTP (0.1 mg/nostril) intranasally once before the drug treatment to induce PD. On day 42, the animals were subjected to various behavioral paradigms. Post-treatment with BFT for 42 days significantly improved the motor and nonmotor fluctuations of MPTP. The results demonstrated that treatment with BFT ameliorated MPTP-induced disorders in behavior, body balance, and dopamine levels in the mid-brain. Among the post-treated groups, a high dose of BFT was the most effective treatment. Mean values are indicated in ±SEM, n = 5***(p < 0.001) when compared with the vehicle control, n = 5 ### (p < 0.001) when compared with the disease control; (p < 0.001) when compared with the BFT per se; (p < 0.001) when compared with the low dose of BFT; (p < 0.001) when compared with the high dose of BFT. Our finding suggests that BFT contributed to superior antioxidant, and anti-inflammatory and could be a novel therapeutic method for PD management. In conclusion, BFT could be a potential drug candidate for curbing and preventing PD.

Exploring the influence of the microbiome on the pharmacology of anti-asthmatic drugs.

The microbiome is increasingly implicated in playing a role in physiology and pharmacology; in this review, we investigate the literature on the possibility of bacterial influence on the pharmacology of anti-asthmatic drugs, and the potential impact this has on asthmatic patients. Current knowledge in this area of research reveals an interaction between the gut and lung microbiome and the development of asthma. The influence of microbiome on the pharmacokinetics and pharmacodynamics of anti-asthmatic drugs is limited; however, understanding this interaction will assist in creating a more efficient treatment approach. This literature review highlighted that bioaccumulation and biotransformation in the presence of certain gut bacterial strains could affect drug metabolism in anti-asthmatic drugs. Furthermore, the bacterial richness in the lungs and the gut can influence drug efficacy and could also play a role in drug response. The implications of the above findings suggest that the microbiome is a contributing factor to an individuals' pharmacological response to anti-asthmatic drugs. Hence, future directions for research should follow investigating how these processes affect asthmatic patients and consider the role of the microbiome on drug efficacy and modify treatment guidelines accordingly.

Prenatal Cannabinoid Exposure Elicits Memory Deficits Associated with Reduced PSA-NCAM Expression, Altered Glutamatergic Signaling, and Adaptations in Hippocampal Synaptic Plasticity.

Cannabis is now one of the most commonly used illicit substances among pregnant women. This is particularly concerning since developmental exposure to cannabinoids can elicit enduring neurofunctional and cognitive alterations. This study investigates the mechanisms of learning and memory deficits resulting from prenatal cannabinoid exposure (PCE) in adolescent offspring. The synthetic cannabinoid agonist WIN55,212-2 was administered to pregnant rats, and a series of behavioral, electrophysiological, and immunochemical studies were performed to identify potential mechanisms of memory deficits in the adolescent offspring. Hippocampal-dependent memory deficits in adolescent PCE animals were associated with decreased long-term potentiation (LTP) and enhanced long-term depression (LTD) at hippocampal Schaffer collateral-CA1 synapses, as well as an imbalance between GluN2A- and GluN2B-mediated signaling. Moreover, PCE reduced gene and protein expression of neural cell adhesion molecule (NCAM) and polysialylated-NCAM (PSA-NCAM), which are critical for GluN2A and GluN2B signaling balance. Administration of exogenous PSA abrogated the LTP deficits observed in PCE animals, suggesting PSA mediated alterations in GluN2A- and GluN2B- signaling pathways may be responsible for the impaired hippocampal synaptic plasticity resulting from PCE. These findings enhance our current understanding of how PCE affects memory and how this process can be manipulated for future therapeutic purposes.

Phenyl-2-aminoethyl selenide ameliorates hippocampal long-term potentiation and cognitive deficits following doxorubicin treatment.

Chemotherapy-induced memory loss ("chemobrain") can occur following treatment with the widely used chemotherapeutic agent doxorubicin (DOX). However, the mechanisms through which DOX induces cognitive dysfunction are not clear, and there are no commercially available therapies for its treatment or prevention. Therefore, the aim of this study was to determine the therapeutic potential of phenyl-2-aminoethyl selenide (PAESe), an antioxidant drug previously demonstrated to reduce cardiotoxicity associated with DOX treatment, against DOX-induced chemobrain. Four groups of male athymic NCr nude (nu/nu) mice received five weekly tail-vein injections of saline (Control group), 5 mg/kg of DOX (DOX group), 10 mg/kg PAESe (PAESe group), or 5 mg/kg DOX and 10 mg/kg PAESe (DOX+PAESe group). Spatial memory was evaluated using Y-maze and novel object location tasks, while synaptic plasticity was assessed through the measurement of field excitatory postsynaptic potentials from the Schaffer collateral circuit. Western blot analyses were performed to assess hippocampal protein and phosphorylation levels. In this model, DOX impaired synaptic plasticity and memory, and increased phosphorylation of protein kinase B (Akt) and extracellular-regulated kinase (ERK). Co-administration of PAESe reduced Akt and ERK phosphorylation and ameliorated the synaptic and memory deficits associated with DOX treatment.

Validating the anti-lymphoma pharmacodynamic actions of the endocannabinoids on canine non-Hodgkin lymphoma.

AIMS: This study established the in vitro anti-lymphoma pharmacodynamic actions of the endocannabinoids (anandamide-AEA and 2-arachidonoylglycerol-2AG) on canine non-Hodgkin lymphoma (NHL) and human NHL cells. MAIN METHODS: The expression of cannabinoid (CB1 and CB2) receptors in various canine NHL cells {1771, CLBL-1, CLL-1, peripheral blood mononuclear cells (PBMCs)} was studied using Quantitative real-time PCR (RT-qPCR). Anti-lymphoma cell viability assay was performed to assess the effect of endocannabinoids on various canine and human NHL cells (1771, CLBL-1, CLL-1, Ramos cells). The spectrophotometric and fluorometric procedures evaluated oxidative stress, inflammation, apoptosis, and mitochondrial function markers. SAS® and Prism-V La Jolla, CA, USA, were used for statistical analysis. KEY FINDINGS: The current study validated the presence of CB1 and CB2 receptors in the canine NHL cells. There was a significantly higher expression of CB1 and CB2 receptors in B-cell lymphoma (BCL) cells (1771, CLBL-1, Ramos) compared to canine T-cell lymphoma (TCL) cells (CL-1). AEA and 2AG dose and time-dependently exhibited significant but differential anti-lymphoma effects on canine and human NHL cells. Anti-lymphoma pharmacodynamic actions of the endocannabinoids in the canine 1771 NHL cells revealed a significant alteration in the markers of oxidative stress, inflammation, and a decrease in mitochondrial function without altering the apoptotic markers. SIGNIFICANCE: Establishing the anti-lymphoma pharmacodynamic actions of endocannabinoids may provide new therapeutic interventions and expedite cannabinoid research.

Oxidative stress and COVID-19-associated neuronal dysfunction: mechanisms and therapeutic implications.

Severe acute respiratory syndrome (SARS)-CoV-2 virus causes novel coronavirus disease 2019 (COVID-19), and there is a possible role for oxidative stress in the pathophysiology of neurological diseases associated with COVID-19. Excessive oxidative stress could be responsible for the thrombosis and other neuronal dysfunctions observed in COVID-19. This review discusses the role of oxidative stress associated with SARS-CoV-2 and the mechanisms involved. Furthermore, the various therapeutics implicated in treating COVID-19 and the oxidative stress that contributes to the etiology and pathogenesis of COVID-19-induced neuronal dysfunction are discussed. Further mechanistic and clinical research to combat COVID-19 is warranted to understand the exact mechanisms, and its true clinical effects need to be investigated to minimize neurological complications from COVID-19.

Clinical outcomes of chemotherapy in cancer patients with different ethnicities.

BACKGROUND: Choosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized chemotherapy protocols in place, protocol changes made after extensive clinical trials demonstrate significant improvement in the efficacy and tolerability of certain drugs. The pharmacokinetics, pharmacodynamics, and tolerance of anti-cancer medications are all highly individualized. A driving force behind these differences lies within a person's genetic makeup. RECENT FINDINGS: Pharmacogenomics, the study of how an individual's genes impact the processing and action of a drug, can optimize drug responsiveness and reduce toxicities by creating a customized medication regimen. However, these differences are rarely considered in the initial determination of standardized chemotherapeutic protocols and treatment algorithms. Because pharmacoethnicity is influenced by both genetic and nongenetic variables, clinical data highlighting disparities in the frequency of polymorphisms between different ethnicities is steadily growing.  Recent data suggests that ethnic variations in the expression of allelic variants may result in different pharmacokinetic properties of the anti-cancer medication. In this article, the clinical outcomes of various chemotherapy classes in patients of different ethnicities were reviewed. CONCLUSION: Genetic and nongenetic variables contribute to the interindividual variability in response to chemotherapeutic drugs. Considering pharmacoethnicity in the initial determination of standard chemotherapeutic protocols and treatment algorithms can lead to better clinical outcomes of patients of different ethnicities.

Effects of developmental exposures to Bisphenol-A and Bisphenol-S on hepatocellular function in male Long-Evans rats.

Bisphenol-S (BPS) is a current substitute for Bisphenol-A (BPA) in various commercial products (paper, plastics, protective can-coatings, etc.) used by all age groups globally. The current literature indicates that a drastic surge in pro-oxidants, pro-apoptotic, and pro-inflammatory biomarkers in combination with diminished mitochondrial activity can potentially decrease hepatic function leading to morbidity and mortality. Consequently, there are increasing public health concerns that substantial Bisphenol-mediated effects may impact hepatocellular functions, particularly in newborns exposed to BPA and BPS postnatally. However, the acute postnatal impact of BPA and BPS and the molecular mechanisms affecting hepatocellular functions are unknown. Therefore, the current study investigated the acute postnatal effect of BPA and BPS on the biomarkers of hepatocellular functions, including oxidative stress, inflammation, apoptosis, and mitochondrial activity in male Long-Evans rats. BPA and BPS (5 and 20 microgram/Liter (µg/L) of drinking water) were administered to 21-day-old male rats for 14 days. BPS had no significant effect on apoptosis, inflammation, and mitochondrial function but significantly reduced the reactive oxygen species (51-60 %, **p < 0.01) and nitrite content (36 %, *p < 0.05), exhibiting hepatoprotective effects. As expected, based on the current scientific literature, BPA induced significant hepatoxicity, as seen by significant glutathione depletion (50 %, *p < 0.05). The in-silico analysis indicated that BPS is effectively absorbed in the gastrointestinal tract without crossing the blood-brain barrier (whereas BPA crosses the blood-brain barrier) and is not a substrate of p-Glycoprotein and Cytochrome P450 enzymes. Thus, the current in-silico and in vivo findings revealed that acute postnatal exposure to BPS had no significant hepatotoxicity.

Role of cGAS-Sting Signaling in Alzheimer's Disease.

There is mounting evidence that the development of Alzheimer's disease (AD) interacts extensively with immunological processes in the brain and extends beyond the neuronal compartment. Accumulation of misfolded proteins can activate an innate immune response that releases inflammatory mediators and increases the severity and course of the disease. It is widely known that type-I interferon-driven neuroinflammation in the central nervous system (CNS) accelerates the development of numerous acute and chronic CNS diseases. It is becoming better understood how the cyclic GMP-AMP synthase (cGAS) and its adaptor protein Stimulator of Interferon Genes (STING) triggers type-I IFN-mediated neuroinflammation. We discuss the principal elements of the cGAS-STING signaling pathway and the mechanisms underlying the association between cGAS-STING activity and various AD pathologies. The current understanding of beneficial and harmful cGAS-STING activity in AD and the current treatment pathways being explored will be discussed in this review. The cGAS-STING regulation offers a novel therapeutic opportunity to modulate inflammation in the CNS because it is an upstream regulator of type-I IFNs.

Topical Delivery of Diacetyl Boldine in a Microemulsion Formulation for Chemoprotection against Melanoma.

This study aimed to develop a microemulsion formulation for topical delivery of Diacetyl Boldine (DAB) and to evaluate its cytotoxicity against melanoma cell line (B16BL6) in vitro. Using a pseudo-ternary phase diagram, the optimal microemulsion formulation region was identified, and its particle size, viscosity, pH, and in vitro release characteristics were determined. Permeation studies were performed on excised human skin using Franz diffusion cell assembly. The cytotoxicity of the formulations on B16BL6 melanoma cell lines was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. Two formulation compositions were selected based on the higher microemulsion area of the pseudo-ternary phase diagrams. The formulations showed a mean globule size of around 50 nm and a polydispersity index of <0.2. The ex vivo skin permeation study demonstrated that the microemulsion formulation exhibited significantly higher skin retention levels than the DAB solution in MCT oil (Control, DAB-MCT). Furthermore, the formulations showed substantially higher cytotoxicity toward B16BL6 cell lines than the control formulation (p < 0.001). The half-maximal inhibitory concentrations (IC50) of F1, F2, and DAB-MCT formulations against B16BL6 cells were calculated to be 1 µg/mL, 10 µg/mL, and 50 µg/mL, respectively. By comparison, the IC50 of F1 was 50-fold lower than that of the DAB-MCT formulation. The results of the present study suggest that microemulsion could be a promising formulation for the topical administration of DAB.

Neurotrophin mimetics and tropomyosin kinase receptors: a futuristic pharmacological tool for Parkinson's.

Parkinson's disease is a complex age-related progressive dopaminergic neurodegenerative disease consistently viewed as a disorder of movement and is characterized by its cardinal motor symptoms. While the motor symptoms and its clinical manifestations are attributed to the nigral dopaminergic neuronal death and basal ganglia dysfunction, studies have subsequently proven that the non-dopaminergic neurons in various brain regions are also additionally involved with the disease progression. Thus, it is now well accepted that the involvement of various neurotransmitters and other ligands accounts for the non-motor symptoms (NMS) associated with the Parkinson's disease. Consequently, this has demonstrated to possess remarkable clinical concerns to the patients in terms of various disability, such impaired to compromised quality of life and increased risk of morbidity and mortality. Currently, available pharmacological, non-pharmacological, and surgical therapeutic strategies neither prevent, arrest, nor reverse the nigral dopaminergic neurodegeneration. Thus, there is an imminent medical necessity to increase patient's quality of life and survival, which in turn decreases the incidence and prevalence of the NMS. The current research article reviews the potential direct involvement of neurotrophin and its mimetics to target and modulate neurotrophin-mediated signal transduction pathways to enlighten a new and novel therapeutic strategy along with the pre-existing treatments for Parkinson's disease and other neurological/neurodegenerative disorders which are associated with the downregulation of neurotrophins.

Nutraceuticals: unlocking newer paradigms in the mitigation of inflammatory lung diseases.

Persistent respiratory tract inflammation contributes to the pathogenesis of various chronic respiratory diseases, such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. These inflammatory respiratory diseases have been a major public health concern as they are the leading causes of worldwide mortality and morbidity, resulting in heavy burden on socioeconomic growth throughout these years. Although various therapeutic agents are currently available, the clinical applications of these agents are found to be futile due to their adverse effects, and most patients remained poorly controlled with a low quality of life. These drawbacks have necessitated the development of novel, alternative therapeutic agents that can effectively improve therapeutic outcomes. Recently, nutraceuticals such as probiotics, vitamins, and phytochemicals have gained increasing attention due to their nutritional properties and therapeutic potential in modulating the pathological mechanisms underlying inflammatory respiratory diseases, which could ultimately result in improved disease control and overall health outcomes. As such, nutraceuticals have been held in high regard as the possible alternatives to address the limitations of conventional therapeutics, where intensive research are being performed to identify novel nutraceuticals that can positively impact various inflammatory respiratory diseases. This review provides an insight into the utilization of nutraceuticals with respect to their molecular mechanisms targeting multiple signaling pathways involved in the pathogenesis of inflammatory respiratory diseases.

Critical Clinical Evaluation of COVID-19 Patients with Tuberculosis in the Indian Sub-Continent.

BACKGROUND: COVID-19 and tuberculosis (TB) are infectious diseases that predominantly affect the respiratory system with common symptoms, such as cough, fever, and shortness of breath, making them dual burdens. METHODS: This review will discuss the characteristics of the coexistence of TB and new infectious illnesses to provide a framework for addressing the current epidemic. Currently, there are no clear and significant data on COVID-19 infection in TB patients, they may not respond appropriately to drug therapy and may have worse treatment outcomes, especially if their TB treatment is interrupted. Due to emergence, measurements should be taken to minimize TB and COVID-19 transmission in communal settings and health care institutions were created. For both TB and COVID-19, accurate diagnostic testing and well-designed, and established therapeutic strategies are required for effective treatment. RESULTS: Several health care organizations and networks have specimen transit methods that can be utilized to diagnose and monitor the etiology and progression of COVID 19 and perform contact tracing in developed and underdeveloped nations. Furthermore, patients and health care programs could benefit from increased use of digital health technology, which could improve communication, counseling, treatment, and information management, along with other capabilities to improve health care. CONCLUSION: Patients with COVID-19 pulmonary/respiratory problems may seek treatment from respiratory physicians, pulmonologists, TB experts, and even primary health care workers. To have prophylactic and therapeutic strategies against COVID-19, TB patients should take the appropriate health care measures recommended by health care professionals/government officials and maintain their TB therapy as indicated.

Hispolon Cyclodextrin Complexes and Their Inclusion in Liposomes for Enhanced Delivery in Melanoma Cell Lines.

Hispolon, a phenolic pigment isolated from the mushroom species Phellinus linteus, has been investigated for anti-inflammatory, antioxidant, and anticancer properties; however, low solubility and poor bioavailability have limited its potential clinical translation. In this study, the inclusion complex of hispolon with Sulfobutylether-ß-cyclodextrin (SBEßCD) was characterized, and the Hispolon-SBEßCD Complex (HSC) was included within the sterically stabilized liposomes (SL) to further investigate its anticancer activity against melanoma cell lines. The HSC-trapped-Liposome (HSC-SL) formulation was investigated for its sustained drug delivery and enhanced cytotoxicity. The inclusion complex in the solid=state was confirmed by a Job's plot analysis, molecular modeling, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Proton nuclear magnetic resonance (NMR) spectroscopy, and scanning electron microscopy (SEM). The HSC-SL showed no appreciable deviation in size (<150 nm) and polydispersity index (<0.2) and improved drug encapsulation efficiency (>90%) as compared to control hispolon liposomes. Individually incorporated hispolon and SBEßCD in the liposomes (H-CD-SL) was not significant in loading the drug in the liposomes, compared to HSC-SL, as a substantial amount of free drug was separated during dialysis. The HSC-SL formulation showed a sustained release compared to hispolon liposomes (H-SLs) and Hispolon-SBEßCD liposomes (H-CD-SLs). The anticancer activity on melanoma cell lines (B16BL6) of HSC and HSC-SL was higher than in H-CD-SL and hispolon solution. These findings suggest that HSC inclusion in the HSC-SL liposomes stands out as a potential formulation approach for enhancing drug loading, encapsulation, and chemotherapeutic efficiency of hispolon and similar water insoluble drug molecules.

Health influence of SARS-CoV-2 (COVID-19) on cancer: a review.

The novel coronavirus, namely, SARS-CoV-2 (COVID-19), broke out two years ago and has caused major global health issues. Adequate treatment options are still lacking for the management of COVID-19 viral infections. Many patients afflicted with COVID-19 may range from asymptomatic to severe symptomatic, triggering poor clinical outcomes, morbidity, and mortality. Cancer is one of the leading causes of death worldwide. It is pertinent to re-examine cancer prevalence during the COVID-19 pandemic to prevent mortality and complications. Understanding the impact of SARS-CoV-2 on cancer is key to appropriate healthcare measures for the treatment and prevention of this vulnerable population. Data was acquired from PubMed using key search terms. Additional databases were utilized, such as the Centers for Disease Prevention and Control, American Cancer Society (ACS), and National Cancer Institute (NCI). Cancer patients are more prone to SARS-CoV-2 infection and exhibit poor health outcomes, possibly due to a chronic immunosuppressive state and anticancer therapies. Male sex, older age, and active cancer disease or previous cancer are risk factors for COVID-19 infection, leading to possible severe complications, including morbidity or mortality. The speculated mechanism for potentially higher mortality or COVID-19 complications is through reduced immune system function and inflammatory processes through cancer disease, anticancer therapy, and active COVID-19 infection. This review includes prostate, breast, ovarian, hematologic, lung, colorectal, esophageal, bladder, pancreatic, cervical, and head and neck cancers. This review should help better maintain the health of cancer patients and direct clinicians for COVID-19 prevention to improve the overall health outcomes.

Tissue repair strategies: What we have learned from COVID-19 in the application of MSCs therapy.

Coronavirus disease 2019 (COVID-19) infection evokes severe proinflammatory storm and pulmonary infection with the number of confirmed cases (more than 200 million) and mortality (5 million) continue to surge globally. A number of vaccines (e.g., Moderna, Pfizer, Johnson/Janssen and AstraZeneca vaccines) have been developed over the past two years to restrain the rapid spread of COVID-19. However, without much of effective drug therapies, COVID-19 continues to cause multiple irreversible organ injuries and is drawing intensive attention for cell therapy in the management of organ damage in this devastating COVID-19 pandemic. For example, mesenchymal stem cells (MSCs) have exhibited promising results in COVID-19 patients. Preclinical and clinical findings have favored the utility of stem cells in the management of COVID-19-induced adverse outcomes via inhibition of cytokine storm and hyperinflammatory syndrome with coinstantaneous tissue regeneration capacity. In this review, we will discuss the existing data with regards to application of stem cells for COVID-19.

Sukkari dates seed improves type-2 diabetes mellitus-induced memory impairment by reducing blood glucose levels and enhancing brain cholinergic transmission: In vivo and molecular modeling studies.

Cognitive decline is one of the serious complications associated with diabetes mellitus (T2DM) of type-2. In this reported work, the effect of aqueous sukkari dates seed extract (ASSE) was evaluated in T2DM-induced rats. T2DM was induced using intraperitoneal injection of nicotinamide and streptozocin (STZ) administration. The diabetic rats were then treated orally with 200 mg/kg and 400 mg/kg of dates seed extract for 30 days and results were compared with metformin-treated groups. The memory functions were assessed using three maze models. Glucose and insulin levels in the blood and acetylcholine, acetylcholinesterase brain homogenates were estimated. The results showed a significant reduction in transfer latency (TL) (p < 0.001) during the elevated plus maze (EPM) test. The novel object recognition (NOR) test revealed a longer exploration time (p > 0.05) with novel objects and a higher discrimination index (p > 0.05). The Y-maze test also showed a significant increase in the number of entries to the novel arm (p > 0.05) and the total number of entries in the trial (p > 0.01) as well as in test (p > 0.05) sessions. Reduction in blood glucose (p > 0.05) and improvement in blood insulin (p > 0.05) levels were also noted. Improvement in ACh levels (p > 0.001) with 400 mg/kg of ASSE and reduction in AChE (p > 0.001) with both doses of ASSE were also observed in the brain homogenates. The results of ASSE were found comparable with the metformin-treated rats. The estimation of phytochemical constituents displayed a significant presence of phenolic content. Further, molecular modeling studies showed ellagic acid, catechin, and epicatechin as the potential molecule interacting with GSK-3ß, α-amylase, and AChE and may be responsible for observed bioactivity. In conclusion, ASSE has the ability to alleviate T2DM-related cognitive impairments.