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Abstract Primary hypothyroidism (PHT) is associated with an increased risk for the development of atherosclerosis (AS) and other cardiovascular disorders. PHT induces atherosclerosis (AS) through the induction of endothelial dysfunction, and insulin resistance (IR). PHT promotes vasoconstriction and the development of hypertension. However, patients with subclinical PHT with normal thyroid hormones (THs) are also at risk for cardiovascular complications. In subclinical PHT, increasing thyroid stimulating hormone (TSH) levels could be one of the causative factors intricate in the progression of cardiovascular complications including AS. Nevertheless, the mechanistic role of PHT in AS has not been fully clarified in relation to increased TSH. Therefore, in this review, we discuss the association between increased TSH and AS, and how increased TSH may be involved in the pathogenesis of AS. In addition, we also discuss how L-thyroxine treatment affects the development of AS.

Abstract Atherosclerosis (AS) formation is enhanced by different mechanisms including cytokine generation, vascular smooth muscle cell proliferation, and migration. One of the recent treatments towards endothelial dysfunction and AS is Vinpocetine (VPN). VPN is a potent inhibitor of phosphodiesterase enzyme 1 (PDE-1) and has anti-inflammatory and antioxidant effects through inhibition the expression of nuclear factor kappa B (NF-κB). VPN has been shown to be effective against the development and progression of AS. However, the underlying molecular mechanism was not fully clarified. Consequently, objective of the present review was to discuss the mechanistic role of VPN in the pathogenesis AS. Most of pro-inflammatory cytokines that released from macrophages are inhibited by action of VPN through NF-κB-dependent mechanism. VPN blocks monocyte adhesion and migration by constraining the expression and action of pro-inflammatory cytokines. As well, VPN is effective in reducing of oxidative stress a cornerstone in the pathogenesis of AS through inhibition of NF-κB and PDE1. VPN promotes plaque stability and prevents the erosion and rupture of atherosclerotic plaque. In conclusion, VPN through mitigation of inflammatory and oxidative stress, and improvement of plaque stability effects could be effective agent in the management of AS.

Abstract Apple is an important fruit crop that is always in demand due to its commercial and nutraceutical value. Also, the requirement for quality planting material for this fruit crop for new plantations is increasing continuously. In-vitro propagation is an alternative approach, which may help to produce genetically identical high grade planting material. In this study, for the first time, an efficient and reproducible propagation protocol has been established for apple root stock MM 104 via axillary bud. Culturing axillary buds on Murashige and Skoog apple rootstock (MM 104) resulted in better in-vitro propagation. (MS) basal medium supplemented with 3.0% (w/v) sucrose and 0.8% (w/v) agar. The axillary buds were established in MS basal medium with BA (5.0 µM), NAA (1.0 µM) and further used to establish invitro propagation protocol. Plant Growth Regulators (PGRs), BA (1.0 µM) in combination with NAA (1.0 µM) was found most efficient for shoot multiplication (100%) and produced 9.8 shoots/explants with an average shoot length of (2.4 ± cm). All the shoots produced roots in 0.1 µM IBA with a 5-day dark period. Acclimatization of in-vitro raised plantlets was obtained with vermiculite: perlite: sand: soil (2:2:1:1) resulting in 76% survival under field conditions. The study showed that the use of axillary bud is efficient for multiple-shoot production of apple rootstock (MM 104). This is the first comprehensive report on in-vitro growth of apple root stock MM 104 with an assessment of genetic stability using DNA fingerprinting profiles based on Inter Simple Sequence Repeats (ISSR) and Start Codon Targeted (SCoT). The genetic stability of in-vitro-produced plants, as determined by SCoT and ISSR primers, demonstrated genetic closeness to the mother plant.

Abstract Background Atherosclerosis (AS) is a progressive disease that interferes with blood flow, leading to cardiovascular complications such as hypertension, ischemic heart disease, ischemic stroke, and vascular ischemia. The progression of AS is correlated with inflammation, oxidative stress, and endothelial dysfunction. Various signaling pathways, like nuclear erythroid‐related factor 2 (Nrf2) and Kruppel‐like factor 2 (KLF2), are involved in the pathogenesis of AS. Nrf2 and KLF2 have anti‐inflammatory and antioxidant properties. Thus, activation of these pathways may reduce the development of AS. Metformin, an insulin‐sensitizing drug used in the management of type 2 diabetes mellitus (T2DM), increases the expression of Nrf2 and KLF2. AS is a common long‐term macrovascular complication of T2DM. Thus, metformin, through its pleiotropic anti‐inflammatory effect, may attenuate the development and progression of AS. Aims Therefore, this review aims to investigate the possible role of metformin in AS concerning its effect on Nrf2 and KLF2 and inhibition of reactive oxygen species (ROS) formation. In addition to its antidiabetic effect, metformin can reduce cardiovascular morbidities and mortalities compared to other antidiabetic agents, even with similar blood glucose control by the Nrf2/KLF2 pathway activation. Conclusion In conclusion, metformin is an effective therapeutic strategy against the development and progression of AS, mainly through activation of the KLF2/Nrf2 axis.

Epilepsy is a common neurological disease characterized by the recurrent, paroxysmal, and unprovoked seizures. It has been shown that hyperuricemia enhances and associated with the development and progression of epilepsy through induction of inflammation and oxidative stress. In addition, uric acid is released within the brain and contributes in the development of neuronal hyperexcitability and epileptic seizure. Brain uric acid acts as damage associated molecular pattern (DAMP) activates the immune response and induce the development of neuroinflammation. Therefore, inhibition of xanthine oxidase by allopurinol may reduce hyperuricemia-induced epileptic seizure and associated oxidative stress and inflammation. However, the underlying mechanism of allopurinol in the epilepsy was not fully elucidated. Therefore, this review aims to revise from published articles the link between hyperuricemia and epilepsy, and how allopurinol inhibits the development of epileptic seizure.

Abstract Parkinson's disease (PD) is a progressive neurodegenerative disease as a result of the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The fundamental features of PD are motor and non-motor symptoms. PD symptoms develop due to the disruption of dopaminergic neurotransmitters and other neurotransmitters such as γ-aminobutyric acid (GABA). The potential role of GABA in PD neuropathology concerning the motor and non-motor symptoms of PD was not precisely discussed. Therefore, this review intended to illustrate the possible role of GABA in PD neuropathology regarding motor and non-motor symptoms. The GABA pathway is essential in regulating the inhibitory tone to prevent excessive stimulation of the cerebral cortex. Degeneration of dopaminergic neurons in PD is linked with reducing GABAergic neurotransmission. Decreasing GABA activity promotes mitochondrial dysfunction and oxidative stress, which are highly related to PD neuropathology. Hence, restoring GABA activity by GABA agonists may attenuate the progression of PD motor symptoms. Therefore, dysregulation of GABAergic neurons in the SNpc contributes to developing PD motor symptoms. Besides, PD non-motor symptoms are also related to the dysfunction of the GABAergic pathway, and amelioration of this pathway may reduce PD non-motor symptoms. In conclusion, the deregulation of the GABAergic pathway in PD might be intricate in developing motor and non-motor symptoms. Improving this pathway might be a novel, beneficial approach to control PD symptoms.

Abstract Multiple sclerosis (MS) is the most frequent inflammatory and demyelinating disease of the central nervous system (CNS). The underlying pathophysiology of MS is the destruction of myelin sheath by immune cells. The formation of myelin plaques, inflammation, and injury of neuronal myelin sheath characterizes its neuropathology. MS plaques are multiple focal regions of demyelination disseminated in the brain's white matter, spinal cords, deep grey matter, and cerebral cortex. Fenofibrate is a peroxisome proliferative activated receptor alpha (PPAR-α) that attenuates the inflammatory reactions in MS. Fenofibrate inhibits differentiation of Th17 by inhibiting the expression of pro-inflammatory signaling. According to these findings, this review intended to illuminate the mechanistic immunoinflammatory role of fenofibrate in mitigating MS neuropathology. In conclusion, fenofibrate can attenuate MS neuropathology by modulating different pathways, including oxidative stress, autophagy, mitochondrial dysfunction, inflammatory-signaling pathways, and neuroinflammation.

Abstract COVID-19 appeared as a highly contagious disease after its outbreak in December 2019 by the virus, named SARS-CoV-2. The threat, which originated in Wuhan, China, swiftly became an international emergency. Among different genomic products, spike protein of virus plays a crucial role in the initiation of the infection by binding to the human lung cells, therefore, SARS-CoV-2’s spike protein is a promising therapeutic target. Using a combination of a structure-based virtual screening and biochemical assay, this study seeks possible therapeutic candidates that specifically target the viral spike protein. A database of ~ 850 naturally derived compounds was screened against SARS-CoV-2 spike protein to find natural inhibitors. Using virtual screening and inhibitory experiments, we identified acetyl 11-keto-boswellic acid (AKBA) as a promising molecule for spike protein, which encouraged us to scan the rest of AKBA derivatives in our in-house database via 2D-similarity searching. Later 19 compounds with > 85% similarity with AKBA were selected and docked with receptor binding domain (RBD) of spike protein. Those hits declared significant interactions at the RBD interface, best possess and excellent drug-likeness and pharmacokinetics properties with high gastrointestinal absorption (GIA) without toxicity and allergenicity. Our in-silico observations were eventually validated by in vitro bioassay, interestingly, 10 compounds (A3, A4, C3, C6A, C6B, C6C, C6E, C6H, C6I, and C6J) displayed significant inhibitory ability with good percent inhibition (range: > 72–90). The compounds C3 (90.00%), C6E (91.00%), C6C (87.20%), and C6D (86.23%) demonstrated excellent anti-SARS CoV-2 spike protein activities. The docking interaction of high percent inhibition of inhibitor compounds C3 and C6E was confirmed by MD Simulation. In the molecular dynamics simulation, we observed the stable dynamics of spike protein inhibitor complexes and the influence of inhibitor binding on the protein’s conformational arrangements. The binding free energy ΔGTOTAL of C3 (−38.0 ± 0.08 kcal/mol) and C6E (−41.98 ± 0.08 kcal/mol) respectively indicate a strong binding affinity to Spike protein active pocket. These findings demonstrate that these molecules particularly inhibit the function of spike protein and, therefore have the potential to be evaluated as drug candidates against SARS-CoV-2.

This study aims to use hot aqueous extract of herbal residue (HRE) to enhance bacterial growth and possess anti-diarrheal effects. In this study, lactobacillus species L. brevis (SAM-1), Lactobacillus plantarum (SAM-2), and Lactobacillus herbinensis (SAM-3) were isolated from date palm sap (collected in winter season). Square Pharmaceuticals PLC, Bangladesh provided herbal residues ‘Adovas’ which is non-sedating herbal cough syrup with sixteen common herbs including Adhatoda vasica. In our observation, HRE increased the number of colonies in MRS media. In the anti-diarrheal study by castor oil and magnesium sulphate-induced diarrheal mouse model, SAM-1 and 2 with or without HRE showed almost similar results. After initial morphological characterization, tests such as resistance to low pH, bile salt and survival capability in gastric simulated fluid (GSF) were performed to confirm them as a probiotic candidate. All three isolates were gram-positive bacteria and could grow in a mesophilic range of temperatures. The isolates were catalase-negative and were able to coagulate milk after overnight incubation. As the isolates exhibited resistance to low pH and could tolerate bile salts, they may survive in the stomach and intestine, thus making them a promising probiotic candidate. The isolated probiotics and HRE inhibited diarrheal and restored the body's electrolytes. Interestingly, SAM-2 showed higher efficacy than the standard drug (Loperamide), while SAM-1 showed a similar effect and SAM-3, had less effect than Loperamide. The findings suggest that probiotics and herbal residue could contribute to diarrhoeal disease prevention, which might be an alternative to a synthetic standard drug (Loperamide).

The continual increase in global diabetic statistics portends decreased productivity and life spans, thus making it a disease of concern requiring more effective and safe therapeutic options. While several reports on antidiabetic plants, including Hura crepitans, are available, there is still a dearth of information on the holistic antidiabetic properties of H. crepitans and its associated complications. This study evaluated the antidiabetic potential of methanolic extract of Hura crepitans using in vitro, in vivo, and in silico approaches. The extract revealed a dose-dependent in vitro effect, with a 47.97 % and 65.34 % decrease in the fasting blood sugar levels of streptozotocin (STZ) induced diabetic rats at 150 and 300 mg/kg BW, respectively. Likewise, the extract increased serum and pancreatic insulin levels, and significantly ameliorated neuronal oxidative stress and inflammation by reducing the expression levels of cholinesterase, NF-κB, and COX-2 in the brain of hyperglycemic rats. Serum dyslipidemia, liver, and kidney biomarker indices, and hematological alterations in diabetic rats were also significantly attenuated by the extract. Several constituents, mainly terpenes, were identified in the extract. To further predict the drug-likeness, pharmacokinetics, and binding properties of the compounds, in silico analysis was conducted. Ergosta-2,24-dien-26-oicacid,18-(acetyloxy)-5,6-epoxy-4, 22-dihydroxy-1-oxo-,delta.-lactone-4.beta., displayed the highest docking scores for acetylcholinesterase, butyrylcholinesterases, alpha-amylase, and nuclear factor-kB with values of −12.4, −10.9, −10.3, and −9.4 kcal/mol, while ergost-25-ene-6,12-dione,3,5-dihydroxy-, (3.beta.,5.alpha.) topped for cyclooxygenase-2 (-9.0 kcal/mol). The top-ranked compounds also presented significant oral drug-likeness, pharmacokinetics, and safety properties. Altogether, our data provide preclinical evidence of the potential of Hura crepitans in ameliorating diabetes and its associated complications.

A series of six unsymmetrical thiourea derivatives, namely 1-cyclohexyl-3-(pyridin-2-yl) thiourea (1), 1-cyclohexyl-3-(3-methylpyridin-2-yl)thiourea (2), 1-cyclohexyl-3-(2,4-dimethylphenyl) thiourea (3), 1-(4-chlorophenyl)-3-cyclohexylthiourea (4), 1-(3-methylpyridin-2-yl)-3-phenylthiourea (5), and 1-(3-chlorophenyl)-3-phenylthiourea (6), were successfully synthesized via reaction between different amines with isothiocyanates under a non-catalytic environment. Structural elucidation of compounds (1–6) was performed using FT-IR and NMR (1H and 13C) spectroscopy. The infrared spectra displayed characteristic stretching vibrations, while the 13C NMR chemical shifts of the thiourea moiety (CS) were observed in the range of 179.1–181.4 ppm. The antioxidative and antimicrobial properties of the compounds were assessed, as well as their inhibitory effects on acetylcholinesterase and butyrylcholinesterase were evaluated. In order to analyze the fluorescence characteristics of each compound (1–6), the excitation (λex) and emission (λem) wavelengths were scanned within the range of 250–750 nm, with the solvent blank serving as a standard. It was observed that when dissolved in acetone, toluene, tetrahydrofuran, and ethyl acetate, these compounds exhibited emission peaks ranging from 367 to 581 nm and absorption peaks ranging from 275 to 432 nm.

Epilepsy is a chronic neurological disorder manifested by recurring unprovoked seizures resulting from an imbalance in the inhibitory and excitatory neurotransmitters in the brain. The process of epileptogenesis involves a complex interplay between the reduction of inhibitory gamma-aminobutyric acid (GABA) and the enhancement of excitatory glutamate. Pro-BDNF/p75 NTR expression is augmented in both glial cells and neurons following epileptic seizures and status epileptics (SE). Over-expression of p75 NTR is linked with the pathogenesis of epilepsy, and augmentation of pro-BDNF/p75 NTR is implicated in the pathogenesis of epilepsy. However, the precise mechanistic function of p75 NTR in epilepsy has not been completely elucidated. Therefore, this review aimed to revise the mechanistic pathway of p75 NTR in epilepsy.

Hepatic lipidosis (HL) is a serious metabolic disorder that affects transient high-producing dairy cows. However, there are many laboratory methods could help in the assessment of HL in dairy cows, the definite diagnosis of the disease under field conditions remains a challenge because of the non-specificity of clinical parameters. The aim of the study was to investigate the utility of serum biomarkers, and ultrasonography (US) measurement to diagnose HL in dairy cows. Forty Holstein dairy cows underwent physical examination and were divided into three groups: non-HL, mild HL, and severe HL groups based on US findings, and the concentrations of beta-hydroxybutyric acid (BHBA) and nonesterified fatty acids (NEFAs). Ultrasound images showed hyperechoic lesions and increased pixel intensity (PI) values of liver echotexture in the HL groups. A significant increase was observed in mild and severe HL groups in the activity of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), BHBA, NEFAs, malondialdehyde (MDA), and nitric oxide (NO) while the concentrations of triglyceride (TG), glutathione (GSH), and total antioxidant capacity (TAC) were significantly decreased. The classification accuracy was in the interest of NEFAs (cut off 0.62 mmol/L, sensitivity 82.6%, specificity 91.7%, and an AUC of 0.913) and BHBA (cut off 1.35 mmol/L, sensitivity 91.31%, specificity of 86.4%, and an AUC 0.812) as important diagnostic parameters. This study offers new insights into the importance of serum biochemical parameters and oxidative stress biomarkers especially, AST, NEFAs, BHBA, and GSH with the digital values of US images for prompt use of minimally invasive techniques to diagnose HL under farm conditions.HIGHLIGHTS Serum metabolites and oxidative stress indices could diagnose hepatic lipidosis in dairy cows NEFA and BHBA concentrations and ultrasound digital values can use as a non-invasive way to the classification of hepatic lipidosis degrees in cows under farm condition.

Abstract This study investigated the dynamics in pyrethriod resistance and the presence/frequencies of L1014F knockdown resistance mutant allelles in Culex quinquefasciatus vector populations from Uruan Local Government Area of AkwaIbom State, Southern Nigeria between the months of March and November, 2021. Uruan LGA is among the endemic LGAs for lymphatic filariasis in AkwaIbomState. Female Anopheles mosquitoes from Eman Uruan, Ituk Mbang and Idu Uruan were exposed to permethrin, deltamethrin and alphacypermethrin in CDC insecticide coated bottles for susceptibility bioassay following standard protocols. The mosquitoes were obtained as aquatic forms from the study sites and reared under laboratory conditions to adults. The adult mosquitoes were used for this study. All the mosquitoes used for the insecticide susceptibility bioassay were morphologically identified. Standard Polymerase chain reaction (PCR) was used for authenticating the Culex quinquefasciatus species. A portion of the vgsc (917 bp) gene spanning the entire intron and the exon containing the L1014F mutation associated with knockdown resistance (kdr) in the vectorswere amplified using Allele-SPECIFIC POLYMERASE CHAIN REACTION (AS-PCR) in order to detect target site insensitivity in the vectors from the study sites. Results obtained revealed that vectors from all the study sites were resistant to permethrin insecticide (mortality rate: 18–23%). Suspected resistance (mortality rate: 90–93%) to deltamethrin and low resistance (mortality rate: 82–85%) to alphacypermethrin insecticides were detected. knockdown was more rapid with deltamethrin and alphacypermethrin than with permethrin across the study sites considering their KDT50 and KDT95. The frequency of the resistant phenotypes ranged from 35.14 to 55.3% across the study sites with a net of 45.1% resistant phenotype recorded in this study. The 1014F allelic frequency calculated from Hardy–Weinberg principle for vector populations across the study sites ranged from 0.500 (50.00%) to 0.7763 (77.63%). All populations witnessed significant (p

Abstract Autophagy is an explicit cellular process to deliver dissimilar cytoplasmic misfolded proteins, lipids and damaged organelles to the lysosomes for degradation and elimination. The mechanistic target of rapamycin (mTOR) is the main negative regulator of autophagy. The mTOR pathway is involved in regulating neurogenesis, synaptic plasticity, neuronal development and excitability. Exaggerated mTOR activity is associated with the development of temporal lobe epilepsy, genetic and acquired epilepsy, and experimental epilepsy. In particular, mTOR complex 1 (mTORC1) is mainly involved in epileptogenesis. The investigation of autophagy’s involvement in epilepsy has recently been conducted, focusing on the critical role of rapamycin, an autophagy inducer, in reducing the severity of induced seizures in animal model studies. The induction of autophagy could be an innovative therapeutic strategy in managing epilepsy. Despite the protective role of autophagy against epileptogenesis and epilepsy, its role in status epilepticus (SE) is perplexing and might be beneficial or detrimental. Therefore, the present review aims to revise the possible role of autophagy in epilepsy.

Abstract Background Obesity is a global health issue arising from the unhealthy accumulation of fat. Medicinal plants such as Alstonia boonei stem bark has been reported to possess body weight reducing effect in obese rats. Thus, this study sought to investigate the in vitro and in silico effects of fractions from Alstonia boonei stem bark on selected obesity-related digestive enzymes and adipogenesis in 3T3-L1 preadipocytes. Method Two fractions were prepared from A. boonei: crude alkaloid fraction (CAF) and crude saponin fraction (CSF), and their phytochemical compounds were profiled using Liquid chromatography with tandem mass spectrometry (LCMS/MS). The fractions were assayed for inhibitory activity against lipase, α-amylase and α-glucosidase, likewise their antiadipogenic effect in 3T3-L1 adipocytes. The binding properties with the 3 enzymes were also assessed using in silico tools. Results Eleven alkaloids and six saponin phytochemical compounds were identified in the CAF and CSF using LCMS/MS. The CAF and CSF revealed good inhibitory activity against pancreatic lipase enzyme, but weak and good activity against amylase respectively while only CSF had inhibitory activity against α-glucosidase. Both fractions showed antiadipogenic effect in the clearance of adipocytes and reduction of lipid content in 3T3-L1 adipocytes. The LCMS/MS identified compounds (41) from both fractions demonstrated good binding properties with the 3 enzymes, with at least the top ten compounds having higher binding energies than the reference inhibitors (acarbose and orlistat). The best two docked compounds to the three enzymes were firmly anchored in the substrate binding pockets of the enzymes. In a similar binding pattern as the reference acarbose, Estradiol-17-phenylpropionate (-11.0 kcal/mol) and 3α-O-trans-Feruloyl-2 α -hydroxy-12-ursen-28-oic acid (-10.0 kcal/mol) interacted with Asp197 a catalytic nucleophile of pancreatic amylase. Estradiol-17-phenylpropionate (-10.8 kcal/mol) and 10-Hydroxyyohimbine (-10.4 kcal/mol) interacted with the catalytic triad (Ser152-Asp176-His263) of pancreatic lipase while Estradiol-17-phenylpropionate (-10.1 kcal/mol) and 10-Hydroxyyohimbine (-9.9 kcal/mol) interacted with Asp616 and Asp518 the acid/base and nucleophilic residues of modelled α-glucosidase. Conclusion The antiobesity effect of A. boonei was displayed by both the alkaloid and saponin fractions of the plant via inhibition of pancreatic lipase and adipogenesis.

Abstract A positive response in reversibility testing is widely used to diagnose patients with airway limitations. However, despite its simple procedure, it doesn’t accurately reflect the exact airway irreversibility. This study aimed to investigate the efficacy of a bronchodilation reversibility test using salbutamol and fluticasone/salmeterol combination in obese non-smoker subjects. The study included patients without a history of obstructive lung disease or bronchodilators. A sub-classification of patients based on body mass index (BMI) was carried out into normal ( 0.05). The magnitude of bronchodilation, as identified by spirometry, following fluticasone/salmeterol was higher in all participants, with a significant increase in obese subjects with a p-value of 0.013, 0.002, and 0.035 for FEV1, FEV1% predicted, and FEV1/FVC, respectively. Fluticasone/salmeterol combination increases FEV1, FEV1% of predicted, and FEV1/FVC ratio than the conventional test using salbutamol inhaler, and it can be a potential candidate for assessment of airway obstruction using reversibility test, especially among the obese population.

Abstract Background Neurodegenerative disorders (NDDs) are associated with increased activities of brain acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoamine oxidase (MAO) as well as Aβ-amyloid (Aβ) neurotoxicity; therefore, they offer a therapeutic option for the treatment of NDDs such as Alzheimer’s disease (AD). This study was aimed at identifying multi-targeting neurotherapeutics from Gongronema latifolium leaves using in vitro analysis, GC–MS profiling and computational methods. Results The n-hexane solvent partition fraction of the methanol extract of Gongronema latifolium leaf (HF) exhibited concentration-dependent inhibitory activities against acetylcholinesterase and butyrylcholinesterase but not against MOA in vitro. The GC–MS chemical profiling identified 17 phytochemicals from the HF; these were further screened against human AChE, BChE, β-secretase enzyme (BACE1) and amyloid-β (Aβ) fibrils using molecular docking, ensemble-based docking (EBD), molecular dynamics simulation (MDs) and binding free energy (BFG) coupled with predictive adsorption, distribution, metabolism, excretion and toxicity (ADMET) analysis. The lead phytochemicals (LPs) (dihydroactinidiolide and 1H-Indole-3-ethanamine), with mean binding energies (− 6.525 ± 0.895 and 6.475 ± 0.985; − 6.833 ± 0.461 and − 6.466 ± 0.577; − 6.2 ± 0.845 and − 5.95 ± 0.353 kcal/mol) exhibited multi-target binding tendencies to the catalytic residues of hAChE, hBChE and hBACE1, in addition to hAβ fibril-disruptive tendencies (− 6.325 ± 0.545 and − 5.95 ± 0.353 kcal/mol), respectively. These results corroborated the initial molecular docking and BFG computations. The lead phytochemical–protein complexes were stable during the period of MDs. The LP presented favorable drug-likeness and ADMET properties coupled with the capacity to traverse the BBB. Conclusion Dihydroactinidiolide and 1H-Indole-3-ethanamine, in part or in synergy, are identified as neurotherapeutic constituents of Gongronema latifolium that may have been responsible for the ethnopharmacologically reported neurotherapeutic activities of the leaf, and hence they are suggested as potential drug candidates that can be useful for managing or treating neurodegenerative disease such as Alzheimer's disease, subject to further investigation.

Trans fatty acids are specific unsaturated fats found in processed foods that undergo hydrogenation, leading to hepatic disorders such as metabolic-associated fatty liver disease (MAFLD) and conditions like CVD and CKD. The effects of different food samples containing trans fatty acids (elaidic and oleic acid) on the liver, heart, and kidney through antioxidant enzyme activity were investigated in animal models. Liver function tests (ALT, ALP, AST, and LDH), heart biomarker levels (CPK, TC, HDL, LDL, and triglycerides), and kidney biomarker levels (serum creatinine, blood urea nitrogen, and serum uric acid) were examined in serum of rabbits and the histopathology of liver tissues. Results showed that these biomarkers were more elevated in the Mujahid Ghee group than in the normal control, oleic acid, and Kausar Ghee groups. The concentration of antioxidant markers such as peroxidase, glutathione, catalase, thiobarbituric acid reactive substances, and superoxide dismutase were lower in the Mujahid Ghee group. HPLC showed that Mujahid Ghee had the highest quantified value of elaidic acid among all selected samples. Overall, this study demonstrated that elaidic acid in its purest form aggravated MAFLD in rabbit livers and provoked CVK and CVD.

Abstract Background Testicular cancer (TC), comprising merely 1% of male neoplasms, holds the distinction of being the most commonly encountered neoplasm among young males. Recent findings Most cases of testicular neoplasms can be classified into two main groups, namely germ cell tumors representing approximately 95% of the cases, and sex cord‐stromal tumors accounting for about 5% of the cases. Moreover, its prevalence is on the rise across the globe. TC is a neoplastic condition characterized by a favorable prognosis. The advent of cisplatin‐based chemotherapeutic agents in the latter part of the 1970s has led to a significant enhancement in the 5‐year survival rate, which presently surpasses 95%. Given that TC is commonly detected before reaching the age of 40, it can be anticipated that these individuals will enjoy an additional 40–50 years of life following successful treatment. The potential causes of TC are multifactorial and related to different pathologies. Accurate identification is imperative to guarantee the utmost efficacious and suitable therapy. To a certain degree, this can be accomplished through the utilization of blood examinations for neoplastic indicators; nonetheless, an unequivocal diagnosis necessitates an evaluation of the histological composition of a specimen via a pathologist. Conclusion TC is multifactorial and has various pathologies, therefore this review aimed to revise the prenatal and postnatal causes as well as novel diagnostic biomarkers and the therapeutic strategies of TC.

Balanites aegyptiaca (B. aegyptiaca) is an African herb with traditional medical applications. Various pathogenic factors cause hepatic fibrosis and require novel treatment alternatives. Nanoformulation-based natural products can overcome the available drug problems by increasing the efficacy of natural products targeting disease markers. The current study investigated B. aegyptiaca methanolic extract using high-pressure liquid chromatography (HPLC), and B. aegyptiaca/chitosan nanoparticles were prepared. In vivo, evaluation tests were performed to assess the curative effect of the successfully prepared B. aegyptiaca/chitosan nanoparticles. For 30 days, the rats were divided into six groups, typical and fibrosis groups, where the liver fibrosis groups received B. aegyptiaca extract, silymarin, chitosan nanoparticles, and B. aegyptiaca/chitosan nanoparticles daily. In the current investigation, phenolic molecules are the major compounds detected in B. aegyptiaca extract. UV showed that the prepared B. aegyptiaca /chitosan nanoparticles had a single peak at 280 nm, a particle size of 35.0 ± 6.0 nm, and a negative charge at − 8.3 mV. The animal studies showed that the synthetic B. aegyptiaca/chitosan nanoparticles showed substantial anti-fibrotic protective effects against CCl4-induced hepatic fibrosis in rats when compared with other groups through optimization of biochemical and oxidative markers, improved histological changes, and modulated the expression of Col1a1, Acta2 and Cxcl9 genes, which manage liver fibrosis. In conclusion, the current research indicated that the prepared B. aegyptiaca/chitosan nanoparticles improved histological structure and significantly enhanced the biochemical and genetic markers of liver fibrosis in an animal model.

Poly-herbal therapies for chronic diseases like diabetes mellitus (DM) have been practiced in south Asia for centuries. One of such therapies comprises of Hordeum vulgare, Elettaria cardamomum and Cicer arietinum that have shown encouraging therapeutic potential in the treatment of diabetes and obesity. Therefore, poly-herbal granules (PHGs) of this formula were developed and investigated for their anti-diabetic and anti-obesity potential in obese-diabetic rats. The developed PHGs were chemical characterized and the virtual molecular docking was performed by Discovery studio visualizer (DSV) software. For in-vivo experiment, obesity in rats was induced with high-fat high-sugar diet. After that, diabetes was induced by alloxan monohydrate 150 mg/kg i.p. injection. The diseased rats were treated with PHGs at 250, 500 and 750 mg/kg/day for four weeks. GC-MS analysis of PHGs demonstrated the presence of 1,3-Benzenedicarboxylic acid bis(2-ethylhexyl) ester and 1,2-Benzenedicarboxylic acid di-isooctyl ester and phenol, 2,4-bis(1,1-dimethylethyl). Molecular docking of these compounds demonstrated higher binding energies with receptor than metformin against α-amylase and α-glucosidase. PHGs exhibited a decline in body weight, HbA1c, hyperlipidemia, hyperglycemia, and insulin resistance in diseased rats. The histopathological examination revealed that PHGs improved the alloxan-induced damage to the pancreas. Furthermore, PHGs increased the SOD, CAT and GSH while and the decreased the level of MDA in the liver, kidney and pancreas of diseased rats. Additionally, the PHGs had significantly downregulated the TNF-α and NF-κB while upregulated the expression of NrF-2. The current study demonstrated that the PHGs exhibited anti-diabetic and anti-obesity potential through amelioration of oxidative stress, NF-κB, TNF-α, and NrF-2 due to the presence of different phytochemicals.

Abstract Background Endometrial adenocarcinoma (EAC) is a malignant tumor of the endometrium. EAC is the most common female malignancy following the menopause period. About 40% of patients with EAC are linked with obesity and interrelated with hypertension, diabetes mellitus, and high circulating estrogen levels. Proprotein convertase (PC) furin was involved in the progression of EAC. Recent findings Furin is a protease enzyme belonging to the subtilisin PC family called PC subtilisin/kexin type 3 that converts precursor proteins to biologically active forms and products. Aberrant activation of furin promotes abnormal cell proliferation and the development of cancer. Furin promotes angiogenesis, malignant cell proliferation, and tissue invasion by malignant cells through its pro‐metastatic and oncogenic activities. Furin activity is correlated with the malignant proliferation of EAC. Higher expression of furin may increase the development of EAC through overexpression of pro‐renin receptors and disintegrin and metalloprotease 17 (ADAM17). As well, inflammatory signaling in EAC promotes the expression of furin with further propagation of malignant transformation. Conclusion Furin is associated with the development and progression of EAC through the induction of proliferation, invasion, and metastasis of malignant cells of EAC. Furin induces ontogenesis in EAC through activation expression of ADAM17, pro‐renin receptor, CD109, and TGF‐β. As well, EAC‐mediated inflammation promotes the expression of furin with further propagation of neoplastic growth and invasion.

[This corrects the article DOI: 10.1371/journal.pone.0293477.].

Abstract Introduction Cancer is a significant public health challenge globally, with nearly 2000 lives lost daily in Africa alone. Without adequate measures, mortality rates are likely to increase. The major challenge for cancer care in Africa is equity and prioritization, as cancer is not receiving adequate attention from policy-makers and strategic stakeholders in the healthcare space. This neglect is affecting the three primary tiers of cancer care: prevention, diagnosis, and treatment/management. To promote cancer care equity, addressing issues of equity and prioritization is crucial to ensure that everyone has an equal chance at cancer prevention, early detection, and appropriate care and follow-up treatment. Methodology Using available literature, we provide an overview of the current state of cancer care in Africa and recommendations to close the gap. Results We highlight several factors that contribute to cancer care inequity in Africa, including inadequate funding for cancer research, poor cancer education or awareness, inadequate screening or diagnostic facilities, lack of a well-organized and effective cancer registry system and access to care, shortage of specialized medical staff, high costs for screening, vaccination, and treatment, lack of technical capacity, poor vaccination response, and/or late presentation of patients for cancer screening. We also provide recommendations to address some of these obstacles to achieving cancer care equity. Our recommendations are divided into national-level initiatives and capacity-based initiatives, including cancer health promotion and awareness by healthcare professionals during every hospital visit, encouraging screening and vaccine uptake, ensuring operational regional and national cancer registries, improving healthcare budgeting for staff, equipment, and facilities, building expertise through specialty training, funding for cancer research, providing insurance coverage for cancer care, and implementing mobile health technology for telemedicine diagnosis. Conclusion Addressing challenges to cancer equity holistically would improve the likelihood of longer survival for cancer patients, lower the risk factors for groups that are already at risk, and ensure equitable access to cancer care on the continent. This study identifies the existing stance that African nations have on equity in cancer care, outlines the current constraints, and provides suggestions that could make the biggest difference in attaining equity in cancer care.

Abstract Type 2 diabetes (T2D) is a metabolic disease caused by the development of insulin resistance (IR), relative insulin deficiency, and hyperglycemia. Hyperglycemia-induced neurochemical dysregulation activates the progression of depression in T2D patients. Therefore, management of depression by antidepressant agents improves glucose homeostasis and insulin sensitivity. However, prolong use of antidepressant drugs may increase the risk for the development of T2D. However, there is strong controversy concerning the use of antidepressant drugs in T2D. Therefore, this review try to elucidate the potential effects of antidepressant drugs in T2D regarding their detrimental and beneficial effects.

Abstract Silver nanoparticles (AgNPs) have been generally used due to their strong antibacterial, antiviral and antifungal and antimicrobial properties. However, their toxicity is a subject of sustained debate, thus requiring further studies. Hence, this study examines the adverse effects of the sub-dermal administered dose of AgNPs (200 nm) on the liver, kidney and heart of male Wistar rats. Thirty male rats were randomly distributed into six groups of five animals per group. Group A and D served as the control and received distilled water for 14 and 28 days respectively. Groups B and C were sub-dermally exposed to AgNPs at 10 and 50 mg/kg daily for 14 days while E and F were sub-dermally exposed to AgNPs at 10 and 50 mg/kg daily for 28 days. The liver, kidney and heart of the animals were collected, processed and used for biochemical and histological analysis. Our results revealed that the subdermal administration of AgNPs induced significant increased (p

Abstract Human Islet amyloid polypeptide (hIAPP) from pancreatic β cells in the islet of Langerhans has different physiological functions including inhibiting the release of insulin and glucagon. Type 2 diabetes mellitus (T2DM) is an endocrine disorder due to relative insulin insufficiency and insulin resistance (IR) is associated with increased circulating hIAPP. Remarkably, hIAPP has structural similarity with amyloid beta (Aβ) and can engage in the pathogenesis of T2DM and Alzheimer’s disease (AD). Therefore, the present review aimed to elucidate how hIAPP acts as a link between T2DM and AD. IR, aging and low β cell mass increase expression of hIAPP which binds cell membrane leading to the aberrant release of Ca2+ and activation of the proteolytic enzymes leading to a series of events causing loss of β cells. Peripheral hIAPP plays a major role in the pathogenesis of AD, and high circulating hIAPP level increase AD risk in T2DM patients. However, there is no hard evidence for the role of brain-derived hIAPP in the pathogenesis of AD. Nevertheless, oxidative stress, mitochondrial dysfunction, chaperon-mediated autophagy, heparan sulfate proteoglycan (HSPG), immune response, and zinc homeostasis in T2DM could be the possible mechanisms for the induction of the aggregation of hIAPP which increase AD risk. In conclusion, increasing hIAPP circulating levels in T2DM patients predispose them to the development and progression of AD. Dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists attenuate AD in T2DM by inhibiting expression and deposition of hIAP.

Abstract Neprilysin (NEP) is a transmembrane zinc‐dependent metalloproteinase that inactivates various peptide hormones including glucagon‐like peptide 1 (GLP‐1). NEP inhibitors may be effective in the management of type 2 diabetes mellitus (T2DM) by increasing the circulating level of GLP‐1. However, acute‐effect NEP inhibitors may lead to detrimental effects by increasing blood glucose independent of GLP‐1. These findings suggest a controversial point regarding the potential role of NEP inhibitors on glucose homeostasis in T2DM patients. Therefore, this perspective aimed to clarify the controversial points concerning the role of NEP inhibitors on glucose homeostasis in T2DM. NEP inhibitors may lead to beneficial effects by inhibition of NEP, which is involved in the impairment of glucose homeostasis through modulation of insulin resistance. NEP increases dipeptidyl peptidase‐4 (DPP4) activity and contributes to increasing active GLP‐1 proteolysis so NEP inhibitors may improve glycemic control through increasing endogenous GLP‐1 activity and reduction of DPP4 activity. Thus, NEP inhibitors could be effective alone or in combination with antidiabetic agents in treating T2DM patients. However, long‐term and short‐term effects of NEP inhibitors may lead to a detrimental effect on insulin sensitivity and glucose homeostasis through different mechanisms including augmentation of substrates and pancreatic amyloid deposition. These findings are confirmed in animal but not in humans. In conclusion, NEP inhibitors produce beneficial rather than detrimental effects on glucose homeostasis and insulin sensitivity in humans though most of the detrimental effects of NEP inhibitors are confirmed in animal studies.

Specific compounds extracted from plants can control insect pests. The objective of this study was to evaluate the toxicity of deodar oil (phytopesticide) to adult mealworms Tenebrio molitor (Coleoptera: Tenebrionidae) compared with carbosulfan (synthetic insecticide), which exibits cholinesterase (ChE), glutamic pyruvic transaminase (GPT), and glutamic oxaloacetic transaminase (GOT) activities. The insecticides were applied through feeding, and the LC50 (lethal concentration) was calculated using the Finney method. The LC50 of deodar oil was higher than that of carbosulfan. The doses of both deodar oil and carbosulfan inhibited the ChE activity (p > 0.05) and enhanced the GPT and GOT activities (p < 0.05) in mealworm adults. Alterations in the activity of these biomarkers indicated that deodar oil could effectively control adult mealworms, being an environmentally low-impact method that can replace the use of chemical products.

Abstract Patients with coronavirus disease 2019 (COVID-19) were shown to have reduced serum testosterone levels compared to healthy individuals. Low testosterone levels are linked with the development of erectile dysfunction (ED). In this case-controlled study, 20 healthy controls and 39 patients with ED 3 months after recovering from mild-to-moderate COVID-19 pneumonia were studied. The patients ranged in age from 31 to 47 years. To identify early and late COVID-19 infections, real-time polymerase-chain reaction (RT-PCR) and COVID-19 antibody testing were done. The levels of luteinizing hormone (LH), follicular stimulating hormone (FSH), total testosterone (TT), free testosterone (FT), free androgenic index (FAI), and sex hormone-binding globulin (SHBG) were measured. The sexual health inventory for patients (SHIM) score was used to measure the erectile function of the patients and controls. When compared to the controls, the TT serum level in long COVID-19 (LC) patients with ED was low (p = 0.01). In contrast to controls, FT and FAI were both lower in LC patients with ED. (p = 0.001). FSH serum levels did not significantly differ (p = 0.07), but in ED patients, LH serum levels were elevated. SHIM scores were associated with low TT (p = 0.30), FT (p = 0.09), and high LH (p = 0.76) in LC patients with ED. Male patients with decreased serum levels of LH and testosterone may have hypothalamic-pituitary–gonadal axis dysfunction, which could lead to the development of LC-induced ED. Therefore, an in-depth research is necessary to confirm the causal link between COVID-19 and ED in LC patients.

Abstract Onchocerciasis is a parasitic disease transmitted by black flies. Human onchocerciasis is a public health and socioeconomic problem in Nigeria. Its prevalence and morbidity have reduced over the years because of control efforts especially, Mass Drug Administration with ivermectin. The current goal is to eliminate the disease transmission by 2030. Understanding the changes in transmission patterns in Cross River State is critical to elimination of onchocerciasis in Nigeria. This study was designed to determine the transmission dynamics of onchocerciasis in Cross River State after over two decades of mass ivermectin distribution in endemic communities. Agbokim, Aningeje, Ekong Anaku and Orimekpang are four endemic communities from three Local Government Areas of the State selected for this study. Transmission indices such as infectivity rates, biting rates and transmission potentials, parity rates and diurnal biting activities were determined. A total of 15,520 adult female flies were caught on human baits, Agbokim (2831), Aningeje (6209), Ekong Anaku (4364) and Orimekpang (2116). A total of 9488 and 5695 flies were collected during the rainy and dry seasons respectively in the four communities studied. The differences in relative abundance among the communities were statistically significant (P

Diabetic retinopathy (DR) is a form of retinal microangiopathy that occurs as a result of long-term Diabetes mellitus (DM). Patients with Diabetes mellitus typically suffer from DR as a progression of the disease that may be due to initiation and dysregulation of pathways like the polyol, hexosamine, the AGE/RAGE, and the PKC pathway, which all have negative impacts on eye health and vision. In this review, various databases, including PubMed, Google Scholar, Web of Science, and Science Direct, were scoured for data relevant to the aforementioned title. The three most common therapies for DR today are retinal photocoagulation, anti-vascular endothelial growth factor (VEGF) therapy, and vitrectomy, however, there are a number of drawbacks and limits to these methods. So, it is of critical importance and profound interest to discover treatments that may successfully address the pathogenesis of DR. Curcumin and β-glucogallin are the two potent compounds of natural origin that are already being used in various nutraceutical formulations for several ailments. They have been shown potent antiapoptotic, anti-inflammatory, antioxidant, anticancer, and pro-vascular function benefits in animal experiments. Their parent plant species have been used for generations by practitioners of traditional herbal medicine for the treatment and prevention of various eye ailments. In this review, we will discuss about pathophysiology of Diabetic retinopathy and the therapeutic potentials of curcumin and β-glucogallin one of the principal compounds from Curcuma longa and Emblica officinalis in Diabetic retinopathy.

Polycystic ovary syndrome (PCOS) is a common hormonal disorder that affects women of reproductive age and is characterized by multiple ovarian cysts, irregular menstrual cycles, and excessive androgen hormone production. The present study aimed to investigate the therapeutic efficacy of melatonin in alleviating PCOS-induced alterations in female Wistar rats. PCOS was induced in female albino rats by administering letrozole at a dose of 1 mg/kg for 21 days. A total of 24 rats were randomly selected and divided into four groups: group I (normal control), group II (melatonin treatment), group III (letrozole treatment), and group IV (melatonin therapy for PCOS rats). Physical parameters (body and uterus weight), hormone profile (LH and FSH), and steroidogenic enzyme activities and an oral glucose test were assessed using standard methods. Histological analysis was performed using hematoxylin and eosin staining. The results demonstrated that exogenous melatonin administration significantly improved PCOS symptoms in rats, including reduced body weight gain, changes in organ weight/body weight index, blood glucose level, percentage diestrus phase, testosterone, estradiol, progesterone, and LH/FSH ratio, as well as 3β-HSD and 17β-HSD enzyme activity. Histopathological findings revealed well-developed follicles, decreased cystic follicles, and increased antral follicles, Graafian follicles, and corpus luteum in PCOS rats treated with melatonin. These positive outcomes suggest that exogenous melatonin may hold promise as a valuable remedy for PCOS conditions in female rats. Further research is warranted to fully elucidate the underlying mechanisms and potential clinical applications of melatonin in the context of PCOS.

Abstract Background: Coronavirus disease 2019 (COVID‐19) is a pandemic disease caused by severe acute respiratory syndrome CoV type 2 (SARS‐CoV‐2). COVID‐19 is higher in men than women and sex hormones have immune‐modulator effects during different viral infections, including SARS‐CoV‐2 infection. One of the essential sex hormones is progesterone (P4). Aims: This review aimed to reveal the association between P4 and Covid‐19. Results and Discussion: The possible role of P4 in COVID‐19 could be beneficial through the modulation of inflammatory signaling pathways, induction of the release of anti‐inflammatory cytokines, and inhibition release of pro‐inflammatory cytokines. P4 stimulates skew of naïve T cells from inflammatory Th1 toward anti‐inflammatory Th2 with activation release of anti‐inflammatory cytokines, and activation of regulatory T cells (Treg) with decreased interferon‐gamma production that increased during SARS‐CoV‐2 infection. In addition, P4 is regarded as a potent antagonist of mineralocorticoid receptor (MR), it could reduce MRs that were activated by stimulated aldosterone from high AngII during SARS‐CoV‐2. P4 active metabolite allopregnanolone is regarded as a neurosteroid that acts as a positive modulator of γ‐aminobutyric acid (GABAA) so it may reduce neuropsychiatric manifestations and dysautonomia in COVID‐19 patients. Conclusion: Taken together, the anti‐inflammatory and immunomodulatory properties of P4 may improve central and peripheral complications in COVID‐19.

Clivia miniata (Lindl) is a member of the family Amaryllidaceae known for its chemically diverse alkaloids with a wide range of biological activities. Many reports revealed a direct role of oxidative stress in the early stage of Alzheimer’s disease (AD). Meanwhile, β-site amyloid precursor protein cleavage enzyme 1 (BACE-1) is a molecular target for the treatment of AD. We aimed to investigate C. miniata root, bulb, and aerial part chemical profiling, antioxidant, BACE-1, and AChE enzyme inhibitory activities. Results showed that the total root had the most potent radical scavenging activity as compared to the total bulb and aerial part, respectively. Ethanol root extract had the most potent BACE-1 inhibitory activity (IC50 = 0.02 ± 0.001 µg/mL) as compared to the bulb and aerial part (IC50 = 0.93 ± 0.13, 1.80 ± 0.24 µg/mL), respectively. Moreover, the total root extract mitigated AChE enzyme activity more than total bulb and aerial fractions with IC50 values of (0.06 ± 0.02, 0.58 ± 0.3, and 1.89 ± 0.42 µg/mL, respectively. Bioassay-guided acid-base fractionation confirmed superior BACE-1 inhibitory activity of the root fractions particularly, methylene chloride and ethyl acetate fractions with (IC50 values of 0.21 ± 0.60 and 0.01 ± 0.001 µg/mL), respectively. UPLC-MS analysis of ethyl acetate and methylene chloride fractions of C. miniata root led to the identification of eight phenolics and thirteen alkaloids, respectively. Molecular docking studies against BACE-1 protein revealed that lycorine di-hexoside, miniatine, and cliviaaline were the most promising hits. Further investigation of anti-AD potential of the aforementioned small molecules is required.

Abstract Heparanase (HPSE) is an endoglycosidase cleaves heparan sulfate (HS) and this contributes to the degradation and remodeling of the extracellular matrix. HS cleaved by HPSE induces activation of autophagy and formation of autophagosommes which facilitate binding of HPSE to the HS and subsequent release of growth factors. The interaction between HPSE and HS triggers releases of chemokines and cytokines which affect inflammatory response and cell signaling pathways with development of hyperinflammation, cytokine storm (CS) and coagulopathy. HPSE expression is induced by both SARS-CoV-2 and monkeypox virus (MPXV) leading to induction release of pro-inflammatory cytokines, endothelial dysfunction and thrombotic events. Co-infection of MPX with SARS-CoV-2 may occur as we facing many outbreaks of MPX cases during Covid-19 pandemic. Therefore, targeting of HPSE by specific inhibitors may reduce the risk of complications in both SARS-CoV-2 and MPXV infections. Taken together, HPSE could be a potential link between MPX with SARS-CoV-2 in Covid-19 era.

Abstract Monkeypox (MPX) is a common zoonotic disease caused by a double-strand DNA MPX virus (MPXV). MPX was considered a sporadic rare disease causing a mild disease with a low capacity to spread among humans. The clinical picture of human MPX highly resembles smallpox, though early lymphadenopathy in human MPX is the distinguishing sign not present in smallpox. The incubation period is 1–3 weeks, and fever, headache, joint pain, myalgia, and nausea for about 3 days. Skin lesions that appear 1–3 days following fever and lymphadenopathy usually appear simultaneously on the face and periphery. By cross-reactivity and protection, the smallpox vaccine produced 85% protection against infection with Orthopoxviruses, including MPX. Antiviral drugs like tecovirimate and brincidofovir could be effective agents against the development of MPX. MPX epidemics are less reported and described as other life-threatening epidemics, leading to an unclear picture of this disease’s pathogenesis, epidemiology, and management. With the recent wide range of MPX outbreaks, immense research is mandatory to revise the importance of MPX pathogenesis and risk for epidemic development worldwide. Therefore, this critical study aimed to review MPX's pathogenesis, epidemiology, and management with possible repurposed drugs.

The objective of the present work was to develop and optimize an intranasal in situ gel of Pramipexole dihydrochloride for enhanced drug delivery, better patient acceptability, and possible proper treatment of Parkinson’s disease. Preliminary studies were performed to select formulation components and identify key variables affecting the formulation. The optimization of the in situ gelling system of Pramipexole dihydrochloride was achieved by applying 32 full factorial design using Design-Expert® software (Stat-Ease 9.0.6 version) and taking concentrations of Poloxamer 407 (X1) and HPMC K4M (X2) as independent variables. The gelling temperature, gel strength, and percentage of drug diffused after 8 h were taken as dependent variables. The software provided an optimized formulation, with 16.50% of X1 and 0.2% of X2 with the highest desirability. An in vivo drug retention time study was performed for the optimized formulation in Wistar rats. The results of the optimization process demonstrated that the selected gel formulation exhibited desirable characteristics, including gelation near body temperature, good gel strength, suitable viscosity, and sustained drug release. The optimized formulation displayed significantly higher drug retention, lasting about 5 h, versus the plain poloxamer gel formulation. Hence, it was concluded that the optimized formulation will remain affixed at the site of application for a significant time after intranasal administration and consequently sustain the release of the drug. The optimized formulation was found to be stable during the stability studies. The developed dosage form may improve patient compliance, enhance nasal drug residence, and offer sustained drug release. However, further clinical studies are necessary to validate these findings.

Abstract A novel coronavirus (CoV) known as severe acute respiratory syndrome CoV type 2 is the causative agent for the development of CoV disease 2019 (Covid‐19). Covid‐19 may increase the risk of developing pulmonary histoplasmosis due to immune dysregulation. In addition, Covid‐19 may enhance the propagation of acute pulmonary histoplasmosis due to lung injury and inflammation, and using corticosteroids in severely affected Covid‐19 patients may reactivate latent pulmonary histoplasmosis. Likewise, activation of inflammatory signaling pathways during H. capsulatum infection may increase the severity of Covid‐19 and vice versa. Furthermore, lymphopenia in Covid‐19 may increase the risk for the progress of pulmonary histoplasmosis besides activation of inflammatory signaling pathways during H. capsulatum infection may increase the severity of Covid‐19 and vice versa. Therefore, this critical review aimed to find the potential link between Covid‐19 pneumonia and pulmonary histoplasmosis concerning the immunological response.

Diabetes mellitus is a rapidly spreading global metabolic disorder that has serious social, health, and economic consequences. Herein, we have evaluated in vivo antidiabetic and antihyperlipidemic effects of myrrhanone-B and myrrhanol-B (isolated from Commiphora mukul Hook). We observed that treatment with myrrhanone-B and myrrhanol-B at a dose of 5 and 10 mg/kg body weight for 21 days significantly improved body weight loss, water consumption, and the concentration of blood glucose level (BGL) in alloxan (120 mg/kg) induced diabetic mice, which indicates that the compounds possess strong anti-diabetic activities. In the biochemical analysis, these compounds improved an abnormal level of total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein cholesterol (LDL-C) to a normal level and increased the high-density lipoprotein cholesterol level (HDLC). Later, drug target of compounds was predicted through in-silico docking which shows that these compounds nicely fit in the active site of α-glucosidase enzyme and mediates excellent interactions with the catalytic residues, Asp214 and Asp349. The in-silico results were confirmed by in-vitro testing of myrrhanone-B and myrrhanol-B against α-glucosidase where both the compounds exhibited excellent inhibitory potency with IC50 values of 19.50 ± 0.71, and 16.11 ± 0.69 µM, respectively. Furthermore, mechanistic study was conducted to observe their binding mechanism, which reflect that myrrhanol-B has mixed type of inhibition (ki = 12.33 ± 0.030 µM), while myrrhanone-B demonstrates competitive type of inhibition (ki =14.53 ± 0.040 µM).

Paris polyphylla Smith (Melanthiaceae) family, which is native to the Himalayan region, has received a lot of attention recently due to its extensive history of usage in traditional medicine. The production of steroidal saponin from callus suspension cultures of P. polyphylla was observed in the current study. The current study attempted to develop a P. polyphylla plant callus suspension culture through optimization of cultivation technique for callus suspension, quantification of total phenolic components and estimation of the extract’s antioxidant activity. A light-yellow callus was formed within six weeks of cultivating rhizomes on Murashige and Skoog (MS) media supplemented with Thidiazuron (TDZ). Furthermore, the effect of TDZ, Methyl Jasmonate (MeJA), and Yeast Extract (YE) on callus growth, steroidal saponin (dioscin and diosgenin), total phenolic content, total flavonoids, total tannin, and total antioxidant activity was also measured. The medium containing 0.5 μM TDZ depicted the maximum callus biomass (2.98 g fresh weight). Significantly high phenolic and tannin content was observed in the MS medium containing 50 μM MeJA, whereas, no significant increase was observed in total tannin production in any treatment. Three in vitro assays, DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azino-bis (3-ethylbenzothiazoline- 6-sulfonic acid)) and FRAP (ferric ion reducing antioxidant potential) and FC (Folin-Ciocalteu), were used to assess antioxidant potential of callus. Maximum antioxidant analysis reported in 1.0 μM TDZ (6.89 mM AAE/100 g) containing medium followed by 50 μM MeJA (6.44 mM AAE/100 g). The HPLC analysis showed a high presence of dioscin and diosgenin (5.43% and 21.09%, respectively) compared to the wild sample (2.56% and 15.05%, respectively). According to the results, callus produced on media supplemented with 50 μM MeJA have significant phenolic contents and elevated antioxidant activity; nevertheless, callus growth was greater in the presence of 0.5 μM TDZ. The findings of the current study have commercial implications since greater biomass production will result in active phytochemicals that the pharmaceutical and nutraceutical sectors are in need desperately.

Abstract Type 2 diabetes mellitus (T2DM) is a chronic endocrine disorder due to the reduction of insulin sensitivity and relative deficiency of insulin secretion. Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor beta (TGF‐β) superfamily and was initially identified as macrophage inhibitory cytokine‐1 (MIC‐1). GDF15 is considered a cytokine with an anti‐inflammatory effect and increases insulin sensitivity, reduces body weight, and improves clinical outcomes in diabetic patients. GDF15 acts through stimulation of glial‐derived neurotrophic factor (GDNF) family receptor α‐like (GFRAL), which is highly expressed in the brain stem to induce taste aversion. Metformin belongs to the group of biguanides that are derived from the plant Galega officinalis. It is interesting to note that metformin is an insulin‐sensitizing agent used as a first‐line therapy for T2DM that has been shown to increase the circulating level of GDF15. Thus, the present review aims to determine the critical association of the GDF15 biomarker in T2DM and how metformin agents affect it. This review illustrates that metformin activates GDF15 expression, which reduces appetite and leads to weight loss in both diabetic and nondiabetic patients. However, the present review cannot give a conclusion in this regard. Therefore, experimental, preclinical, and clinical studies are warranted to confirm the potential role of GDF15 in T2DM patients.

Regarding applied, facile, green chemical research, a bio-inspired approach is being reported for the sonochemical synthesis of Ag nanoparticles by Aloe vera gel extract as a natural reducing/stabilising and solid support agent without using any toxic and harmful reagent. The biosynthesized Ag NPs/A. vera gel bionanocomposite was characterised by advanced physicochemical techniques like ultraviolet-visible (UV–Vis), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), X-ray Diffraction (XRD) and elemental mapping study. It has been established that Aloe vera gel-stabilized silver nanoparticles have a spherical shape with a mean diameter of around 35–40 nm. To investigate the antioxidant potentials of Ag NPs/A. vera gel, one of the common antioxidant techniques i.e. DPPH was used. The results of DPPH test proved the excellent antioxidant properties of Ag NPs/A. vera gel in comparison to the positive control used i.e. butylated hydroxytoluene. The IC50 of Ag NPs/A. vera gel was 42 µg/mL in the antioxidant test. Thereafter, on having a significant IC50 value in radical scavenging assay, we extended the bio-application of the desired nanocomposite in the anticancer study. To survey the cytotoxicity and anti-human cervical carcinoma effects of Ag NPs/A. vera gel, MTT assay was used on CC1-PI19, SiHa, HeLa and HNCF-PI52 cell lines. The IC50 of the Ag NPs/A. vera gel was 16, 13, 15 and 11 µg/mL against CC1-PI19, SiHa, HeLa and HNCF-PI52 cell lines, respectively. As mentioned, the Ag NPs/A. vera gel had significant antioxidant and anti-human cervical cancer effects. After approving the above results in the clinical trial studies, the Ag NPs/A. vera gel can be used as a chemotherapeutic drug for the treatment of several types of cervical cancers. According to the above results, the significant anti-cervical cancer effects of Ag NPs/A. vera gel are confirmed.

Moringa oleifera is a nutrient-rich plant, also referred to as a miracle tree, and is commonly used in the preparation of functional foods including herbal biscuits. Despite having a wide range of biomolecules, M. oleifera has not been studied for its nutritional benefits in Nepal. To fill this gap, five different formulations of flower and leaf powder ratios of 11:4, 11.75:3.25, 12.5:2.5, 13.25:1.75, 14:1 named as A, B, C, D, E, and control formulations were tested for their sensory and chemical characteristics. The results showed that calcium content (115.73 mg/100 g) was higher in biscuits with a higher percentage of the leaf (11:4) while TPC was minimum. Further, biscuits containing a higher percentage of flower powder contained fewer tannins. The sensory analysis concluded that D was deemed the best in overall attributes by panelists upon statistical analysis, however formulations A and B were superior to other samples regarding the chemical properties. These findings confirm that there is a huge potential for improving herbal biscuits.

There is higher energy in the protein content than in other weaning foods; sorghum and millets are utilized as weaning food in Ethiopia, India, Tanzania, Uganda, and several other African countries. Traditional beverages and giant beers made from sorghum seeds have more nutrients than beers made using malt. The chemical composition and mycoflora of dried sorghum bicolor seeds were studied for five-month of storage, and the mycoflora were isolated using different methods. The proximate and mineral analyses were also carried out to show the effect of the hold on the chemical composition of the seeds. During this five-month storage, the fungi isolated were Aspergillus fumigatus, Aspergillus Niger, Botrydioplodia sp., Fusarium sp., Mucor sp., Penicillium sp., and Rhizopus sp. The fungi count of the Sorghum bicolor seeds increased as the month of storage increased. The chemical composition of the Sorghum bicolor seeds decreased as the month of storage increased. Generally, the chemical composition of the freshly prepared seeds were more than those of the stored ones. Ash (2.63 g/100 g sample), fat (3.26 g/100 g sample), Fiber (2.96 g/100 g sample), and the carbohydrate (64.16 g/100 g sample) of the freshly prepared sun-dried Sorghum bicolor seeds were higher than the Ash (2.54 g/100 g sample), fat (2.83 g/100 g sample), and carbohydrate (63.36 g/100 g sample) after 20 weeks of storage. There is a general decrease in the mineral content of the Sorghum bicolor seeds as the month of storage increased.

Key summary points Post-COVID (PCS) syndrome may progress in association with the development of mast cell activation syndrome (MCAS). High D-dimer levels and blood urea nitrogen were observed to be risk factors associated with pulmonary dysfunction in COVID-19 survivors 3 months post-hospital discharge with the development of PCS. Persistence of inflammatory reactions, autoimmune mimicry, and reactivation of pathogens together with host microbiome alterations may contribute to the development of PCS. MCAS is treated by antihistamines, inhibition of synthesis of mediators, inhibition of mediator release, and inhibition of degranulation of mast cells.