Single slice MR image estimation of 3D supraspinatus intramuscular fatty infiltration in older adults: relevance for clinical practice and research.

OBJECTIVE: (1) To compare older adults stratified by supraspinatus tendon tear status (STT status)-no tear (Intact), partial-thickness (PT) tear, full-thickness (FT) tear-by 3D Dixon fat fraction (3D-FF); 2D fat fraction (2D-FF); and 2D Goutallier grade (2D-GG) at the Y-shaped view, and 1.4 cm and 2.8 cm medial to the Y-shaped view. Stratified by STT status to determine (2) correlation of 3D-FF with 2D-FF and 2D-GG and (3) inter-rater reliability at and medial to the Y-shaped view. MATERIALS AND METHODS: Forty-five volunteers ≥ 60 years recruited prospectively received shoulder MRI. 3D-FF and 2D-FF were measured on 6-point-Dixon MRI by three trainees. Goutallier grade was assessed on T1-weighted MRI by three fellowship-trained diagnostic radiologists. Descriptive, reliability, and correlation analyses were performed. RESULTS: Groups showed no difference in age. The FT group showed higher (p < 0.05) mean 3D-FF (14.09% ± 10.99%), mean 2D-FF (1.4 cm medial to Y-shaped view, 14.91% ± 12.11%; 2.8 cm medial to Y-shaped view, 13.32% ± 9.48%), and mean 2D-GG (Y-shaped view, 1.71 ± 0.78; 1.4 cm medial to Y-shaped view, 1.71 ± 0.69; 2.8 cm medial to Y-shaped view, 1.71 ± 0.72), relative to Intact/PT groups. 3D-FF showed strong correlation with 2D-FF among all groups/all analyses (rho, 0.80-0.98; p < 0.001). 3D-FF showed strong correlation with 2D-GG for all FT group analyses (rho, 0.85-0.91; p < 0.05). 3D-FF showed moderate-to-strong correlation considering all Intact/PT group analyses (rho, 0.51-0.79; p < 0.50). Dixon fat fraction showed excellent reliability for all groups (≥ 0.884, intraclass correlation coefficient). Goutallier grade showed excellent reliability for FT group (0.771, weighted Fleiss's kappa) but poor (0.294) and fair (0.502) for Intact and PT groups, respectively. CONCLUSION: Single slice MR image estimation of 3D supraspinatus intramuscular fatty infiltration has merit for continued use in clinical populations requiring potential rotator-cuff-repair surgery. However, Dixon fat fraction should be prioritized for use in research over Goutallier grade due to superior reliability.

An ASER AI/ML expert panel formative user research study for an interpretable interactive splenic AAST grading graphical user interface prototype.

PURPOSE: The AAST Organ Injury Scale is widely adopted for splenic injury severity but suffers from only moderate inter-rater agreement. This work assesses SpleenPro, a prototype interactive explainable artificial intelligence/machine learning (AI/ML) diagnostic aid to support AAST grading, for effects on radiologist dwell time, agreement, clinical utility, and user acceptance. METHODS: Two trauma radiology ad hoc expert panelists independently performed timed AAST grading on 76 admission CT studies with blunt splenic injury, first without AI/ML assistance, and after a 2-month washout period and randomization, with AI/ML assistance. To evaluate user acceptance, three versions of the SpleenPro user interface with increasing explainability were presented to four independent expert panelists with four example cases each. A structured interview consisting of Likert scales and free responses was conducted, with specific questions regarding dimensions of diagnostic utility (DU); mental support (MS); effort, workload, and frustration (EWF); trust and reliability (TR); and likelihood of future use (LFU). RESULTS: SpleenPro significantly decreased interpretation times for both raters. Weighted Cohen's kappa increased from 0.53 to 0.70 with AI/ML assistance. During user acceptance interviews, increasing explainability was associated with improvement in Likert scores for MS, EWF, TR, and LFU. Expert panelists indicated the need for a combined early notification and grading functionality, PACS integration, and report autopopulation to improve DU. CONCLUSIONS: SpleenPro was useful for improving objectivity of AAST grading and increasing mental support. Formative user research identified generalizable concepts including the need for a combined detection and grading pipeline and integration with the clinical workflow.

A review of pomegranate supplementation: A promising remedial avenue for Alzheimer's disease.

Neurodegenerative complications, like Alzheimer's disease (AD) exert adverse effects i.e. psychological and physiological in the central nervous system. The synthetic drugs used for these complications have negative effects on body health and therefore natural remedies are a good and targeted approach to counter such complications. Alternatively, fruits and a variety of biochemicals which are an important source of diet, can be used for remedial purposes. Due to the antioxidant properties of polyphenolic compounds, several companies utilize this property to advertise polyphenol-rich beverages. Pomegranate (Punica granatum L.), is one such fruit that is well known for its medical usage due to its antioxidant properties. In the cuurent study a literature search survey was performed on traditional uses, phytochemicals on pomegranate and their medical applications especaily in neurodegenerative deasese using electronic data bases like PubMed, Google Scholar, Scopus, Science Direct Wikipedia and Springer Nature. Based on previous preclinical and clinical studies, pomegranate juice, extracts, and its bioactive constituents have shown many mitigating properties, including suppression of inflammatory cell signaling, reduction in expression of genes associated with oxidative stress as well as pro-inflammatory cytokines in neurons, decreased production of inflammatory and oxidative stress biomarkers and increased expression of endothelial nitric oxide synthase. It also decreases the expression of soluble amyloid protein procurer ß (sAPPß), ß-secretase and carboxyl terminal fragment ß (CTFß). Similarly, during an in-vivo study on APP/PS1 mice, pomegranate supplementation has been shown to impart cognitive aid by the protection of neurons and triggering neurogenesis through anti-inflammatory signaling pathway. In conclusion, pomegranate supplementation can be a promising source of protection against Alzheimer's disease.

Biocontrol rhizobacteria enhances growth and yield of wheat (Triticum aestivum) under field conditions against Fusarium oxysporum.

The current study aimed to identify the survival of bio-control bacteria with antifungal activity against Fusarium oxysporum and assess their growth promoting activity in wheat crop field conditions. To evaluate the fungicidal activities of isolated bacteria using the dual culture method, both qualitative and quantitative bioassays were performed. Plant Growth Promoting activities such as Indole 3-Acetic Acid (IAA), phosphate solubilization, Hydrogen cyanide (HCN), and Siderophore production were assessed for three biocontrol bacterial isolates (BCB 07, BCB16, and BCB 83) out of 180 with 70% antagonistic activity against Fusarium oxysporum. Chitinase, protease, and cellulase interaction in isolates was also tested. BCB16 was selected as it had 70% antagonist activity against F. oxysporum but also had the highest PGPR (Plant Growth Promoting Rhizobacteria) traits when compared to the other two isolates. BCB16 was also tested for survival in talc powder and in wheat crop field conditions. Even after 4 months in talc powder, the survival rate remained stable. In a wheat crop field, BCB16 reduced the disease incidence of Fusarium oxysporum by 54.38%. When compared to fungus alone treatment, BCB16 increased average yield by 57% alone and 32% in challenged conditions. BCB16 was identified molecularly using the 16s rRNA gene. Bacillus amyloliquefaciens shared 97% of the deduced sequence. The sequence was submitted to genbank and assigned the accession number OM333889. Bacillus amyloliquefaciens has the potential to be used in the field as an alternative to synthetic fungicides against Fusarium oxysporum.

Isolation and characterization of biocontrol bacteria.Molecular Identification of efficient biocontrol bacteria.Survival of biocontrol bacteria in talc powder as carrier material.The Bacillus amyloliquefaciens has plant growth-promoting characteristics.B. amyloliquefaciens reduced the disease incidence of F. oxysporum by 57% in field trials.

Estimating 3D supraspinatus intramuscular fatty infiltration in older adults: a pilot study.

BACKGROUND: A recent report suggests that semi-quantitative two-dimensional Goutallier grade (2D-GG) correlates poorly with quantitative three-dimensional Dixon fat fraction (3D-Dixon-FF) on magnetic resonance imaging (MRI). PURPOSE: To determine whether the finding of poor correlation of supraspinatus 3D-Dixon-FF with 2D-GG is reproducible, and to determine the strength of the correlation of 3D-Dixon-FF with quantitative 2D Dixon fat fraction (2D-Dixon-FF). MATERIAL AND METHODS: Ten adults aged ≥60 years were recruited prospectively received shoulder MRI. 2D-Dixon-FF and 3D-Dixon-FF were measured on 6-point Dixon fat fraction maps. 2D-GG was rated on T1-weighted images. RESULTS: The mean age of participants was 70.7 ± 3.7 years. The mean 3D-Dixon-FF was 8.3% ± 5.7%; the mean 2D-Dixon-FF was 7.3% ± 4.4%; and the mean 2D-GG was 0.9 ± 0.7. There was a strong correlation for 3D-Dixon-FF with 2D-Dixon-FF (rho = 0.90; P < 0.001) and with 2D-GG (rho = 0.73; P = 0.017). Excellent inter-observer reliability was found for Dixon fat fraction (intraclass correlation coefficient = 0.946), which was good for Goutallier grade (weighted kappa = 0.634). CONCLUSION: Supraspinatus 3D-Dixon-FF had a strong correlation with 2D-Dixon-FF and 2D-GG in our study population.

A Review on Therapeutic Potential of Natural Phytocompounds for Stroke.

Stroke is a serious condition that results from an occlusion of blood vessels that leads to brain damage. Globally, it is the second highest cause of death, and deaths from strokes are higher in older people than in the young. There is a higher rate of cases in urban areas compared to rural due to lifestyle, food, and pollution. There is no effective single medicine for the treatment of stroke due to the multiple causes of strokes. Thrombolytic agents, such as alteplase, are the main treatment for thrombolysis, while multiple types of surgeries, such ascraniotomy, thrombectomy, carotid endarterectomy, and hydrocephalus, can be performed for various forms of stroke. In this review, we discuss some promising phytocompounds, such as flavone C-glycoside (apigenin-8-C-ß-D-glucopyranoside), eriodictyol, rosamirinic acid, 6″-O-succinylapigenin, and allicin, that show effectiveness against stroke. Future study paths are given, as well as suggestions for expanding the use of medicinal plants and their formulations for stroke prevention.

Deciphering SARS CoV-2-associated pathways from RNA sequencing data of COVID-19-infected A549 cells and potential therapeutics using in silico methods.

BACKGROUND: Coronavirus (CoV) disease (COVID-19) identified in Wuhan, China, in 2019, is mainly characterized by atypical pneumonia and severe acute respiratory syndrome (SARS) and is caused by SARS CoV-2, which belongs to the Coronaviridae family. Determining the underlying disease mechanisms is central to the identification and development of COVID-19-specific drugs for effective treatment and prevention of human-to-human transmission, disease complications, and deaths. METHODS: Here, next-generation RNA sequencing (RNA Seq) data were obtained using Illumina Next Seq 500 from SARS CoV-infected A549 cells and mock-treated A549 cells from the Gene Expression Omnibus (GEO) (GSE147507), and quality control (QC) was assessed before RNA Seq analysis using CLC Genomics Workbench 20.0. Differentially expressed genes (DEGs) were imported into BioJupies to decipher COVID-19 induced signaling pathways and small molecules derived from chemical synthesis or natural sources to mimic or reverse COVID -19 specific gene signatures. In addition, iPathwayGuide was used to identify COVID-19-specific signaling pathways, as well as drugs and natural products with anti-COVID-19 potential. RESULTS: Here, we identified the potential activation of upstream regulators such as signal transducer and activator of transcription 2 (STAT2), interferon regulatory factor 9 (IRF9), and interferon beta (IFNß), interleukin-1 beta (IL-1ß), and interferon regulatory factor 3 (IRF3). COVID-19 infection activated key infectious disease-specific immune-related signaling pathways such as influenza A, viral protein interaction with cytokine and cytokine receptors, measles, Epstein-Barr virus infection, and IL-17 signaling pathway. Besides, we identified drugs such as prednisolone, methylprednisolone, diclofenac, compound JQ1, and natural products such as Withaferin-A and JinFuKang as candidates for further experimental validation of COVID-19 therapy. CONCLUSIONS: In conclusion, we have used the in silico next-generation knowledge discovery (NGKD) methods to discover COVID-19-associated pathways and specific therapeutics that have the potential to ameliorate the disease pathologies associated with COVID-19.

Antiplatelet response to clopidogrel is associated with a haplotype in CYP2C19 gene in Pakistani patients.

Clopidogrel, an antiplatelet drug, is frequently prescribed to patients diagnosed with ischemic diseases such as those suffering from acute coronary syndromes or ischemic stroke. Despite the drug being effective in majority of the patients, some still experience ischemic events early in the treatment which might be due to poor platelet inhibition. This study aims to investigate the association of cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms, haplotypes as well as a wide range of clinical and demographic variables with platelet aggregation phenotypes to clopidogrel in a Pakistani cohort. The study comprised of a total of 120 patients diagnosed with cardiovascular diseases and were treated with clopidogrel. Antiplatelet response to clopidogrel was monitored by Helena AggRAM (HL-2-1785P) and patients with maximal platelet aggregation more than 50% were categorized as low responders and those with less than 50% as high responders. Our results show that 56.6% of patients were homozygous for the CYP2C19 wild-type allele, 38.3% of patients possessed one copy of the CYP2C19*2 allele and 5% of patients possessed both CYP2C19*2 alleles. No CYP2C19*3 allele was found in our patient cohort. There was no statistically significant difference between the high and low responder groups to clopidogrel in terms of extensive, intermediate and poor metabolizer genotypes. However, haplotype (H1), leukocyte count, random blood glucose, and history of diabetes mellitus was associated with the antiplatelet response to clopidogrel. The prevalence of clopidogrel resistance in our population was in line with that reported for other regional and global populations.

DNA methylation across the tree of life, from micro to macro-organism.

DNA methylation is a process in which methyl (CH3) groups are added to the DNA molecule. The DNA segment does not change in the sequence, but DNA methylation could alter the action of DNA. Different enzymes like DNA methyltransferases (DNMTs) take part in methylation of cytosine/adenine nucleosides in DNA. In prokaryotes, DNA methylation is performed to prevent the attack of phage and also plays a role in the chromosome replication and repair. In fungi, DNA methylation is studied to see the transcriptional changes, as in insects, the DNA methylation is not that well-known, it plays a different role like other organisms. In mammals, the DNA methylation is related to different types of cancers and plays the most important role in the placental development and abnormal DNA methylation connected with diseases like cancer, autoimmune diseases, and rheumatoid arthritis.

Supraspinatus fatty infiltration on MRI among older adults receiving physical therapy as initial management for clinically suspected rotator cuff tear: A pilot study.

Objectives: Rotator cuff (RC) tear is common among adults ≥60 years, with supraspinatus tear most common. Intramuscular fatty infiltration (FI) on imaging is predictive of long-term outcomes following RC tear. Physical therapists routinely diagnose RC tear only by clinical examination since most do not order imaging studies. Thus, there is limited knowledge about FI in older populations receiving physical therapy (PT) for initial management of RC tear. The primary objective of our pilot study is to determine longitudinal differences in supraspinatus FI over time among older adults receiving PT (PT cohort) for initial management of RC tear relative to older adult volunteers (control cohort), and with secondary objective to evaluate longitudinal self-reported shoulder function over time. Material and Methods: This was a prospective longitudinal cohort study. Forty adults, 60-85 years, were enrolled at baseline; one follow-up visit at ≥6 months. Shoulder magnetic resonance imaging and clinical screening for Charlson comorbidity index (CCI), body mass index (BMI), and American Shoulder and Elbow Surgeon (ASES) score were completed at baseline and follow-up visits. Supraspinatus FI was evaluated by 6-point Dixon fat fraction and Goutallier grade. PT (n = 15) and control (n = 25) cohorts were stratified by supraspinatus status: Intact (no tear), partial-thickness tear (PTT), and full-thickness tear (FTT). Comparisons within cohort were performed by Kruskal-Wallis test and between cohorts by Mann-Whitney U-test. Interobserver reliability was performed for Dixon fat fraction and Goutallier grade. Results: PT cohort at baseline showed no difference for age, BMI, CCI, and ASES score; supraspinatus FI was highest for FTT by Goutallier grade (no tear, 0.5 ± 0.5; PTT, 1.1 ± 0.2; and FTT, 1.5 ± 0.5; P = 0.033) and by Dixon fat fraction (no tear, 4.6% ± 1.4%; PTT, 6.1% ± 1.9%; and FTT, 6.7% ± 2.5%; P = 0.430). Control cohort at baseline showed no difference for age, BMI, CCI, and ASES score; supraspinatus FI was highest for supraspinatus FTT by Dixon fat fraction (no tear, 5.8% ± 1.2%; PTT, 7.1% ± 6.3%; and FTT, 21.4% ± 10.4%; P = 0.034) and by Goutallier grade (no tear, 0.8 ± 0.5; PTT, 1.0 ± 0.6; and FTT, 2.4 ± 1.7; P = 0.141). No difference between similar PT and control cohort subgroups at baseline except no tear groups for ASES score (PT cohort, 58.9 ± 8.2; control cohort, 84.0 ± 21.9; P = 0.049). No differences were identified for Δ-Dixon fat fraction and Δ-Goutallier grade over time in the PT and control cohorts. PT cohort no tear subgroup showed significant improvement (P = 0.042) for Δ-ASES score over time relative to PTT and FTT subgroups; no difference for Δ-ASES score over time in the control cohort. Conclusion: Full-thickness RC tear showed higher levels of FI relative to PTT or no tear at baseline. Our pilot study's trend suggested that older adults receiving PT for initial management of RC tear have full-thickness RC tear for shorter duration based on relative lower levels of FI at baseline as compared to older adult volunteers with full-thickness RC tear. Our pilot study also found that older adults in the PT cohort with no tear had superior shoulder functional recovery by ASES score over time relative to full-thickness and PTTs.

Neuroprotective effects of Bhilawanol and Anacardic acid during glutamate-induced neurotoxicity.

Bhilawanol (Bh) and anacardic acid (AA) are two lipid-soluble compounds mostly found in the nut of Semecarpus anacardium (SA). This herb has many medicinal properties including enhancing learning and memory, yet its active compounds have not been studied for neuroprotective effects. We investigated the neuroprotective effects of Bh and AA against glutamate induced cell death in the adrenal pheochromocytoma cell line of rats (PC12 cells). Cell viability, toxicity and calcium influx were determined by MTT assay, LDH release assay and Fluo-3 imaging while apoptosis was assayed by caspase-3 and Bcl-2 gene expression. Our results showed that Bh and AA treatments significantly increased cell viability, reduced cell toxicity and calcium influx in PC12 cells in addition to suppressing the reactive oxygen species. Furthermore, AA treatment decreased caspase-3 expression level whereas both Bh and AA enhanced the expression of anti-apoptotic gene Bcl-2 in PC12 cells. Both compounds potently inhibited acetylcholinesterase enzyme (AChE) in a dose and time dependent manner. These findings suggest that the traditional use of SA may be explained on the basis of both Bh and AA showing neuroprotective potential due to their effects on enhancing cell viability, reducing cell toxicity most probably by reducing excessive calcium influx and suppression of ROS as well as by decreasing the expression of proapoptotic caspase 3 gene and increasing the expression of antiapoptotic gene Bcl2. Traditional use in enhancing learning and memory was justified in part by inhibition of AChE.

Myrrhanone B and Myrrhanol B from resin of Commipohora mukul exhibit hepatoprotective effects in-vivo.

Despite a large number of liver disorders, clinically useful drugs are scarce. Moreover, the available therapies are facing the challenges of efficacy and safety. Commipohora mukul has been used in folk medicine globally for millennia for the treatment of several ailments. The current study was designed to evaluate the possible hepatoprotective activity of Myrrhanone B (MN) and Myrrhanol B (ML) isolated from C. mukul using an animal model. The animals (Swiss albino mice) were segregated into seven groups, each comprising six mice. The first group was treated with normal saline at a dose of 1 ML/kg daily intraperitoneally (i.p.) for one week. The second group was treated with acetaminophen (APAP) (250 mg/kg, i.p.), it was taken as a negative control. Group 3 was used as a positive control (treated with Silymarin (100 mg/kg, i.p.)). While groups 4-7 were used as experimental groups (termed as groups II to IV), which were treated with ML and MN at a dose of 0.6 mg/kg, and 1.2 mg/kg (i.p.) for one week. Subsequently, blood serum and liver tissue samples were collected for biochemical and histopathological analysis. Both compounds significantly improved the levels of liver biomarkers including aspartate transaminase (AST), alkaline phosphatase (ALP), bilirubin, lactate dehydrogenase (LDH), and alanine transaminase (ALT) as compared to the normal saline-treated group in APAP-induced hepatotoxic mice. Moreover, both compounds significantly modulated the expression of oxidative biomarkers including superoxide dismutase (SOD), reduced glutathione (GSH), and catalase (CAT) at the same doses. Additionally, ML and MN showed a remarkable improvement in histological changes with only mild inflammation, mild hemorrhage, no necrosis, and no pyknosis as compared to the control groups. In conclusion, MN and ML exhibited significant hepatoprotective effects in the animal model used in this study.

Vaccine Development against COVID-19: Study from Pre-Clinical Phases to Clinical Trials and Global Use.

As per the World Health Organization (WHO), more than 288 vaccines against COVID-19 are being developed, with an estimated 184 being presently investigated in the pre-clinical phases, while 104 of these vaccine candidates are at various stages of clinical trials. Twelve of these are in the advanced stages of clinical investigation, and promising results in the phase 3 trials have already paved the way for their regulatory approval and subsequent dissemination for global use. Preliminary and interim results of some of these candidate vaccines are being analyzed for public dissemination. Some of these vaccines have already been rolled out to immunize not only the highest risk individuals but also the general population in several countries. Once their safety and efficacy are established, the next limiting step would be their mass manufacturing by the pharmaceutical companies to fulfill the global demand. The challenge of manufacturing billions of doses of high-quality vaccines is under-appreciated at the moment. A massive vaccination drive would be needed to protect people of all ages. The timely and coordinated execution of the vaccination effort would require unprecedented coordination at the national and international levels for generating funds to purchase the required doses of vaccines, fair distribution of doses and managing the mechanics of delivering vaccines throughout the world.

Inter-ethnic genetic variations and novel variant identification in the partial sequences of CYP2B6 gene in Pakistani population.

BACKGROUND: Some single nucleotide polymorphisms (SNPs) in the cytochrome P450 (CYP)2B6 gene lead to decreased enzyme activity and have an impact on drug metabolism. The present study was designed to investigate the patterns of genetic distinction across a hypervariable region of the CYP2B6 gene, known to contain important SNPs, i.e. rs4803419 and rs3745274, among five major ethnic groups of the Pakistani population. METHODS: Arlequin v3.5.DnaSPv6.12. and network 5 resources were used to analyze population genetic variance in the partial CYP2B6 gene sequences obtained from 104 human samples belonging to Punjabi, Pathan, Sindhi, Seraiki and Baloch ethnicities of Pakistan. The partial CYP2B6 gene region analyzed in the current study is previously known to possess important SNPs. RESULTS: The data analyses revealed that genetic variance among samples mainly came from differentiation within the ethnic groups. However, significant genetic variation was also found among the various ethnic groups. The high pairwise Fst genetic distinction was observed between Seraiki and Sindhi ethnic groups (Fst = 0.13392, P-value = 0.026) as well as between Seraiki and Balochi groups (Fst = 0.04303, P-value = -0.0030). However, the degree of genetic distinction was low between Pathan and Punjabi ethnic groups. Some SNPs, including rs3745274 and rs4803419, which are previously shown in strong association with increased plasma Efavirenz level, were found in high frequency. Besides, a novel SNP, which was not found in dbSNP and Ensemble databases, was identified in the Balochi ethnicity. This novel SNP is predicted to affect the CYP2B6 splicing pattern. CONCLUSION: These results may have significant implications in Pakistani ethnicities in the context of drugs metabolized by CYP2B6, especially in Seraiki and Balochi ethnicity. The novel heterogeneous SNP, found in the present study, might lead to altered drug-metabolizing potential of CYP2B6 and, therefore, may be implicated in non-responder phenomenon.

Search for safer and potent natural inhibitors of Parkinson's disease.

After Alzheimer's disease, Parkinson's disease (PD) has taken second place in becoming one of the most commonly occurring neurological diseases being responsible for a number of disabling motor symptoms ranging from bradykinesia, akinesia, tremors to rigidity, that mostly targets the elderly population and severely disrupts their quality of life. The true underlying pathology of PD yet remains a mystery, however, recent advances in the field have pointed towards the production of α-synuclein aggregates, oxidative stress, and an imbalance between levels of acetylcholine and dopamine neurotransmitters in the brain that have been shown to result in loss of coordinated movement. Current treatments of PD include the gold standard dopamine precursor L-dopa, dopamine agonists pergolide and bromocriptine, catechol-o-methyl transferases inhibitors, entacapone and tolcapone and monoamine oxidase inhibitors such as Selegine and Rasagiline amongst several other drugs. While these drugs are successful in treating motor symptoms of the disease, they do so with a plethora of side effects that are especially debilitating to the elderly. In the recent years, a considerable amount of attention has been shifted towards phytocompounds such as flavonoids and green tea catechins due to promising experimental results. In this review, we have compiled phytocompounds that have shown potent activity against some of the most important targets for antiparkinsonian therapy. These compounds have exhibited activities that transcend the limits of simply attenuating mitochondrial oxidative stress and have opened doors to the discovery of novel lead compounds for newer, efficacious antiparkinsonian therapies with wider therapeutic windows.

Estimation of polymorphisms in the drug-metabolizing enzyme, cytochrome P450 2C19 gene in six major ethnicities of Pakistan.

Interindividual differences in cytochrome P450 (CYP) 2C19 activity may result in variations in the therapeutic response to drugs metabolized by this enzyme. Differences at gene level may translate into protein level with consequent impairment of the enzyme activity. As a result patients with such genetic differences might experience undesirable effects or no effect at all. The aim of the present study was to find out the prevalence of allelic and genotype frequencies of low activity variants of CYP2C19 genes in healthy individuals from six distinct ethnicities of Pakistan. Blood sample was taken from healthy volunteers following informed consent. Isolation of the DNA was followed by the PCR amplification and restriction fragment length polymorphism. Selected samples were sequenced by Sanger sequencing. The frequency of major alleles was 84.93% for CYP2C19*2 and 91.85% for CYP2C19*3, while minor allele was present at 15.06% for CYP2C19*2 and 8.14% for CYP2C19*3. For CYP2C19*2, the frequency of *1*1 genotype was 75.80%, *1*2 was 18.27%, and *2*2 was 5.92% whereas for CYP2C19*3, The frequency of *1*1 genotype was 84.19%, *1*3 was 15.30%, and *3*3 was 0.49% in the Pakistani population. A substantial variation in genotype and allelic frequencies was observed in various ethnicities. Our study demonstrates that a significant Pakistani population has at least one minor allele, which indicates a large number of patients potentially being affected by these variations. Especially, a significant genotype frequency of PM suggests implication for the treatment response and severity/frequency of adverse effects in patients receiving drugs metabolized by CYP2C19.

Assessment of clinical variables as predictive markers in the development and progression of colorectal cancer.

Colorectal cancer (CRC) is graded as one of the most common cancer. It accounts for the second leading cause of cancer deaths worldwide. The present study intends to investigate the role and importance of different biochemical variables in the development of colorectal cancer.In this cross-sectional study we recruited ninety-one patients diagnosed with colorectal cancer and fifty-three age-sex matched controls from June 2017 to June 2018. Different variables i.e. SOD, GSH, CAT, MDA, TGF, VEGF, TNF, ILs, MMPs, etc., were estimated with the help of their respective methods. Our findings suggest a significant increase in the levels of different inflammatory and stress-related markers. The NFκB, TGF-ß, VEGFß, 8OHdG, IsoP-2α were significantly found to be increased in patients with colon cancer (0.945 ± 0.067 µg/ml, 18.59 ± 1.53 pg/ml, 99.35 ± 4.29 pg/ml, 21.26 ± 1.29 pg/ml, 102.25 ± 4.25 pg/ml) as compared to controls (0.124 ± 0.024 µg/ml, 8.26 ± 0.88 pg/ml, 49.58 ± 2.62 pg/ml, 0.93 ± 0.29 pg/ml, 19.65 ± 3.19 pg/ml). Notably, the levels of different antioxidants were shown to be significantly lower in patients of colon cancer. The present study concluded that excessive oxidative stress and lipid peroxidation result in a decrease in the antioxidative capacity of cells which may influence diverse signaling cascades including NF-KB, which results in DNA modification and gene transcription that ultimately involved in the progression of colon cancer.

Possible Therapeutic Effects of Adjuvant Quercetin Supplementation Against Early-Stage COVID-19 Infection: A Prospective, Randomized, Controlled, and Open-Label Study.

BACKGROUND: Quercetin, a well-known naturally occurring polyphenol, has recently been shown by molecular docking, in vitro and in vivo studies to be a possible anti-COVID-19 candidate. Quercetin has strong antioxidant, anti-inflammatory, immunomodulatory, and antiviral properties, and it is characterized by a very high safety profile, exerted in animals and in humans. Like most other polyphenols, quercetin shows a very low rate of oral absorption and its clinical use is considered by most of modest utility. Quercetin in a delivery-food grade system with sunflower phospholipids (Quercetin Phytosome®, QP) increases its oral absorption up to 20-fold. METHODS: In the present prospective, randomized, controlled, and open-label study, a daily dose of 1000 mg of QP was investigated for 30 days in 152 COVID-19 outpatients to disclose its adjuvant effect in treating the early symptoms and in preventing the severe outcomes of the disease. RESULTS: The results revealed a reduction in frequency and length of hospitalization, in need of non-invasive oxygen therapy, in progression to intensive care units and in number of deaths. The results also confirmed the very high safety profile of quercetin and suggested possible anti-fatigue and pro-appetite properties. CONCLUSION: QP is a safe agent and in combination with standard care, when used in early stage of viral infection, could aid in improving the early symptoms and help in preventing the severity of COVID-19 disease. It is suggested that a double-blind, placebo-controlled study should be urgently carried out to confirm the results of our study.

Bitter Melon (Momordica charantia L.) Fruit Bioactives Charantin and Vicine Potential for Diabetes Prophylaxis and Treatment.

Natural products are gaining clinical significance in modern day health care systems to prevent diseases. Bitter melon, a health promoting vegetable, is traditionally used for medical nutrition therapy to cure diabetes but to reap maximum health claims, vigilant control of its substances in diet is crucial as part of curative action for effective diabetes management. In the present research, first phase focused on detection of key bioactive components, i.e., charantin and vicine in different parts of its fruit. In the second phase, normal and hyperglycemic Sprague Dawley rats were fed on skin, flesh and whole fruit of bitter melon at 150 and 300 mg/kg body weight and assessed for diabetes prophylaxis and treatment. The highest amount of charantin (0.16 ± 0.02 mg/g) was recorded in flesh while vicine was present in abundance in whole fruit (0.21 ± 0.01 µg/100 g). In normal rats, bitter melon supplementation was helpful in managing the onset of diabetes. Hyperglycemic rats showed diabetic complications including polydipsia, polyuria, glycosuria, renal hypertrophy and increased glomerular filtration rate. However, bitter melon consumption showed significant improvements in these parameters. The most potent dose was 300 mg/kg whole fruit that resulted in 31.64% lowering of blood glucose level and 27.35% increase in insulin level in hyperglycemic rats.

Potential therapeutic natural products against Alzheimer's disease with Reference of Acetylcholinesterase.

Alzheimer's disease (AD), is the most common type of dementia primarily affecting the later years of life. Its prevalence is likely to increase in any aging population and will be a major burden on healthcare system by the mid of the century. Despite scientific and technological breakthroughs in the last 50 years, that have expanded our understanding of the disease on a system, cellular and molecular level, therapies that could stop or slow the progression of the disease are still unavailable. The Food and Drug Administration (FDA), has approved acetylcholinesterase (AChE) inhibitors (donepezil, galantamine, tacrine and rivastigmine) and glutamate receptor antagonist (memantine) for the treatment of AD. In this review we summarize the studies reporting phytocompounds and extracts from medicinal plants that show AChE inhibitory activities and could be of potential benefit in AD. Future research directions are suggested and recommendations made to expand the use of medicinal plants and their formulations to prevent, mitigate and treat AD.