Investigating awareness of artificial intelligence in healthcare among medical students and professionals in Pakistan: a cross-sectional study.

Objective: The purpose of this study is to find out the level of awareness and acceptance of artificial intelligence (AI) in Pakistan's medical community so as to comment on its future in our healthcare system. Methods: A survey consisting of 15 close-ended questions was conducted. The questions inquired about awareness about AI and discovered the opinions of healthcare professionals regarding its benefits and expected problems. The data were analyzed using SPSS version 26, and descriptive statistics for percentage and frequency were computed. χ2 test was used to analyze the subgroups (Significant p value <0.05). Results: A total of 351 participants were included in this study. General familiarity with AI was low. Only 75 (21.3%) participants answered that they had good familiarity with AI, and only 56 (16%) of them had good familiarity with the role of AI in medicine. One hundred sixty-eight (47.9%) participants disagreed that AI would out-compete the physician in the important traits of professionalism. Only 71 (20.2%) participants believed AI to be diagnostically superior to the physician. Two hundred fourteen (61.0%) were worried about completely trusting AI in its decisions, and 204(58.1%) believed that AI systems lacking human traits would not be able to mirror the doctor-patient relationship. Two hundred sixty-one (74.4%) participants believed that AI would be useful in Administrative tasks. A majority, 162 (46.2%), do not believe that AI would replace them. Finally, a huge majority of participants [225 (64.1%)] demanded the integration of AI in Pakistan's healthcare system. Conclusion: This study suggests that a majority of healthcare professionals in Pakistan do not believe that they are sufficiently aware of the role of AI in healthcare. This was corroborated by their answers to various questions regarding the capabilities of AI. This study indicates the need for a more comprehensive ascertainment of healthcare professionals' perceptions regarding the role of Artificial Intelligence in medicine and bridging the gap between doctors and technology to further promote a patient-centred approach to medicine.

Countenance and implication of Β-sitosterol, Β-amyrin and epiafzelechin in nickel exposed Rat: in-silico and in-vivo approach.

The detrimental impact of reactive oxygen species on D.N.A. repair processes is one of the contributing factors to colon cancer. The idea that oxidative stress may be a significant etiological element for carcinogenesis is currently receiving more and more support. The goal of the current study is to evaluate the anti-inflammatory and anticancer activity of three powerful phytocompounds-sitosterol, amyrin, and epiafzelechin-alone and in various therapeutic combinations against colon cancer to identify the critical mechanisms that mitigate nickel's carcinogenic effect. To evaluate the ligand-protein interaction of four selected components against Vascular endothelial growth factor (VEGF), Matrix metalloproteinase-9 (MMP9) inhibitor and Interleukin-10 (IL-10) molecular docking approach was applied using PyRx bioinformatics tool. For in vivo analysis, hundred albino rats were included, divided into ten groups, each containing ten rats of weight 160-200 g. All the groups were injected with 1 ml/kg nickel intraperitoneally per week for three months, excluding the negative control group. Three of the ten groups were treated with ß-sitosterol (100 mg/kg b wt), ß-amyrin (100 mg/kg b wt), and epiafzelechin (200 mg/kg b wt), respectively, for one month. The later four groups were fed with combinatorial treatments of the three phyto compounds for one month. The last group was administered with commercial drug Nalgin (500 mg/kg b wt). The biochemical parameters Creatinine, Protein carbonyl, 8-hydroxydeoxyguanosine (8-OHdG), VEGF, MMP-9 Inhibitor, and IL-10 were estimated using ELISA kits and Glutathione (G.S.H.), Superoxide dismutase (S.O.D.), Catalase (C.A.T.) and Nitric Oxide (NO) were analyzed manually. The correlation was analyzed through Pearson's correlation matrix. All the parameters were significantly raised in the positive control group, indicating significant inflammation. At the same time, the levels of the foresaid biomarkers were decreased in the serum in all the other groups treated with the three phytocompounds in different dose patterns. However, the best recovery was observed in the group where the three active compounds were administered concomitantly. The correlation matrix indicated a significant positive correlation of IL-10 vs VEGF (r = 0.749**, p = 0.009), MMP-9 inhibitor vs SOD (r = 0.748**, p = 0.0 21). The study concluded that the three phytocompounds ß-sitosterol, ß-amyrin, and epiafzelechin are important anticancer agents which can target the cancerous biomarkers and might be used as a better therapeutic approach against colon cancer soon.

The secret hidden in dust: Assessing the potential to use biological and chemical properties of the airborne fraction of soil for provenance assignment and forensic casework.

The airborne fraction of soil (dust) is both ubiquitous in nature and contains localised biological and chemical signatures, making it a potential medium for forensic intelligence. Metabarcoding of dust can yield biological communities unique to the site of interest, similarly, geochemical analyses can uncover elements and minerals within dust that can be matched to a geographic location. Combining these analyses presents multiple lines of evidence as to the origin of dust collected from items of interest. In this work, we investigated whether bacterial and fungal communities in dust change through time and whether they are comparable to soil samples of the same site. We integrated dust metabarcoding into a framework amenable to forensic casework, (i.e., using calibrated log-likelihood ratios) to predict the origin of dust samples using models constructed from both dust samples and soil samples from the same site. Furthermore, we tested whether both metabarcoding and geochemical/mineralogical analyses could be conducted on a single swabbed sample, for situations where sampling is limited. We found both analyses could generate results from a single swabbed sample and found biological and chemical signatures unique to sites. However, we did find significant variation within sites, where this did not always correlate with time but was a random effect of sampling. This variation within sites was not greater than between sites and so did not influence site discrimination. When modelling bacterial and fungal diversity using calibrated log-likelihood ratios, we found samples were correctly predicted using dust 67% and 56% of the time and using soil 56% and 22% of the time for bacteria and fungi communities respectively. Incorrect predictions were related to within site variability, highlighting limitations to assigning dust provenance using metabarcoding of soil.

Cross-sectional study of mammographic breast density of Pakistani women and its association with breast cancer.

OBJECTIVE: To explore if a positive association existed between breast cancer and increased breast density. METHODS: The retrospective cross-sectional study was conducted at Shifa International Hospital, Islamabad and comprised data from July 10, 2018, to July 10, 2020, of all patients who underwent mammography for screening or diagnostic purposes. Data was collected by reviewing patients' charts, and was divided into diagnostic group A and screening group B according to mammography target. Breast Imaging Reporting and Data System category was also noted. Data was analysed using SPSS 21. RESULTS: Of the 1,035 women with mean age 46.8±2.5 years (range: 35-82 years), 928(89.7%) were in group A and 107(10.3%) were in group B Prevalent breast densities overall were category A 67(6.3%), B 349(33.7%), C 530(51.2%) and D 89(8.5%). In group A, a lump was detected in 542(58.4%) patients. Of them, 367(67.7%) lesions were malignant and 175(32.3%) were benign. Breast density and malignant tumours had significant association (p<0.05). CONCLUSIONS: Mammographic breast density wsa found to have a significant association with breast cancer.

A Survey on COVID-19 Data Analysis Using AI, IoT, and Social Media.

Coronaviruses are a well-established and deadly group of viruses that cause illness in both humans and animals. The novel type of this virus group, named COVID-19, was firstly reported in December 2019, and, with the passage of time, coronavirus has spread to almost all parts of the world. Coronavirus has been the cause of millions of deaths around the world. Furthermore, many countries are struggling with COVID-19 and have experimented with various kinds of vaccines to eliminate the deadly virus and its variants. This survey deals with COVID-19 data analysis and its impact on human social life. Data analysis and information related to coronavirus can greatly help scientists and governments in controlling the spread and symptoms of the deadly coronavirus. In this survey, we cover many areas of discussion related to COVID-19 data analysis, such as how artificial intelligence, along with machine learning, deep learning, and IoT, have worked together to fight against COVID-19. We also discuss artificial intelligence and IoT techniques used to forecast, detect, and diagnose patients of the novel coronavirus. Moreover, this survey also describes how fake news, doctored results, and conspiracy theories were spread over social media sites, such as Twitter, by applying various social network analysis and sentimental analysis techniques. A comprehensive comparative analysis of existing techniques has also been conducted. In the end, the Discussion section presents different data analysis techniques, provides future directions for research, and suggests general guidelines for handling coronavirus, as well as changing work and life conditions.

Phytochemical profiling and cytotoxic potential of Arnebia nobilis root extracts against hepatocellular carcinoma using in-vitro and in-silico approaches.

Hepatocellular carcinoma is the fifth most prevalent cancer worldwide. The emergence of drug resistance and other adverse effects in available anticancer options are challenging to explore natural sources. The current study was designed to decipher the Arnebia nobilis (A. nobilis) extracts for detecting phytochemicals, in-vitro evaluation of antioxidative and cytotoxic potentials, and in-silico prediction of potent anticancer compounds. The phytochemical analysis revealed the presence of flavonoids, phenols, tannins, alkaloids, quinones, and cardiac glycosides, in the ethanol (ANE) and n-hexane (ANH) extracts of A. nobilis. ANH extract exhibited a better antioxidant potential to scavenge DPPH, nitric oxide and superoxide anion radicals than ANE extract, which showed better potential only against H2O2 radicals. In 24 h treatment, ANH extract revealed higher cytotoxicity (IC50 value: 22.77 µg/mL) than ANH extract (IC50 value: 46.74 µg/mL) on cancer (HepG2) cells without intoxicating the normal (BHK) cells using MTT assay. A better apoptotic potential was observed in ANH extract (49.10%) compared to ANE extract (41.35%) on HepG2 cells using the annexin V/PI method. GCMS analysis of ANH extract identified 35 phytocompounds, from which only 14 bioactive compounds were selected for molecular docking based on druggability criteria and toxicity filters. Among the five top scorers, deoxyshikonin exhibited the best binding affinities of - 7.2, - 9.2, - 7.2 and - 9.2 kcal/mol against TNF-α, TGF-ßR1, Bcl-2 and iNOS, respectively, followed by ethyl cholate and 2-Methyl-6-(4-methylphenyl)hept-2-en-4-one along with their desirable ADMET properties. The phytochemicals of ANH extract could be used as a promising drug candidate for liver cancer after further validations.

Potential effect of luteolin, epiafzelechin, and albigenin on rats under cadmium-induced inflammatory insult: In silico and in vivo approach.

Introduction: Cadmium(Cd) an industrial poison present abundantly in the environment, causes human toxicity by an inflammatory process. Chronic exposure of cadmium can cause a number of molecular lesions that could be relevant to oncogenesis, through indirect or epigenetic mechanisms, potentially including abnormal activation of oncogenes and suppression of apoptosis by depletion of antioxidants. As induction of cyclooxygenase (COX)-2 is linked to inflammatory processes, use of luteolin, epiafzelechin, and albigenin alone or in different combinations may be used as anti-inflammatory therapeutic agents. Methods: We, herein, performed in silico experiments to check the binding affinity of phytochemicals and their therapeutic effect against COX-2 in cadmium administered rats. Wistar albino rats were given phytochemicals in different combinations to check their anti-inflammatory activities against cadmium intoxication. The level of alanine aminotransferases (ALT), 4-hydroxynonenal (4HNE), 8-hydroxy-2-deoxyguanosine (8-OHdG), tumor necrosis factor-alpha (TNF-α), isoprostanes (IsoP-2α), COX-2, and malondialdehyde (MDA) were estimated with their respective ELISA and spectrophotometric methods. Results: The generated results show that phytocompounds possessed good binding energy potential against COX-2, and common interactive behavior was observed in all docking studies. Moreover, the level of ALT, 4HNE, 8-OHdG, TNF-α, IsoP-2α, malondialdehyde, and COX-2 were significantly increased in rats with induced toxicity compared to the control group, whereas in combinational therapy of phytocompounds, the levels were significantly decreased in the group. Discussion: Taken together, luteolin, epiafzelechin, and albigenin can be used as anti-inflammatory therapeutic agents for future novel drug design, and thus it may have therapeutic importance against cadmium toxicity.

The utility of dust for forensic intelligence: Exploring collection methods and detection limits for environmental DNA, elemental and mineralogical analyses of dust samples.

Environmental DNA (eDNA), elemental and mineralogical analyses of soil have been shown to be specific to their source material, prompting consideration of using the airborne fraction of soil (dust) for forensic intelligence work. Dust is ubiquitous in the environment and is easily transferred to items belonging to a person of interest, making dust analysis an ideal tool in forensic casework. The advent of Massive Parallel Sequencing technologies means metabarcoding of eDNA can uncover bacterial, fungal, and even plant genetic fingerprints in dust particles. Combining this with elemental and mineralogical compositions offers multiple, complementary lines of evidence for tracing the origin of an unknown dust sample. This is particularly pertinent when recovering dust from a person of interest to ascertain where they may have travelled. Prior to proposing dust as a forensic trace material, however, the optimum sampling protocols and detection limits need to be established to place parameters around its utility in this context. We tested several approaches to collecting dust from different materials and determined the lowest quantity of dust that could be analysed for eDNA, elemental composition and mineralogy, whilst still yielding results capable of distinguishing between sites. We found that fungal eDNA profiles could be obtained from multiple sample types and that tape lifts were the optimum collection method for discriminating between sites. We successfully recovered both fungal and bacterial eDNA profiles down to 3 mg of dust (the lowest tested quantity) and recovered elemental and mineralogical compositions for all tested sample quantities. We show that dust can be reliably recovered from different sample types, using different sampling techniques, and that fungi and bacteria, as well as elemental and mineralogical profiles, can be generated from small sample quantities, highlighting the utility of dust for forensic intelligence.

Molecular understanding of the effect of hydrogen on graphene growth by plasma-enhanced chemical vapor deposition.

Plasma-enhanced chemical vapor deposition (PECVD) provides a low-temperature, highly-efficient, and catalyst-free route to fabricate graphene materials by virtue of the unique properties of plasma. In this paper, we conduct reactive molecular dynamics simulations to theoretically study the detailed growth process of graphene by PECVD at the atomic scale. Hydrocarbon radicals with different carbon/hydrogen (C/H) ratios are employed as dissociated precursors in the plasma environment during the growth process. The simulation results show that hydrogen content in the precursors significantly affects the growth behavior and properties of graphene (e.g., the quality of obtained graphene, which is indicated by the number of hexagonal carbon rings formed in the graphene sheets). Moreover, increasing the content of hydrogen in the precursors is shown to reduce the growth rate of carbon clusters, and prevent the formation of curved carbon structures during the growth process. The findings provide a detailed understanding of the fundamental mechanisms regarding the effects of hydrogen on the growth of graphene in a PECVD process.

An audit of foeticide, neonaticide and infanticide: A retrospective study in the Department of Forensic Medicine, King Edward Medical University, Lahore.

The deliberate killing of a foetus in the womb, or a child from the first 24 h of birth to one month of age, or within the first year of life, is called foeticide, neonaticide and infanticide, respectively. Socioeconomic stress, mental illness, gender selection, shame or fear of punishment of adultery or illegitimacy, grudge and jealousy with parents and negligent delivery by dai are major causative factors in such cases. This is a retrospective, descriptive, observational study, and the sample pool consisted of 35 cases. Foeticide cases were 42.9% of the total and the same percentage of cases were neonaticides, while 14.3% of cases were of infanticide. The male-to-female ratio was 1.26:1 and the major cause of death was head injury. The study shows a prevalence of foeticide and neonaticide as compared to infanticide. It also displays the prevalence of males in overall cases and a higher number of unknown cases in our setting.

New challenges in the use of nanomedicine in cancer therapy.

Nanomedicines are applied as alternative treatments for anticancer agents. For the treatment of cancer, due to the small size in nanometers (nm), specific site targeting can be achieved with the use of nanomedicines, increasing their bioavailability and conferring fewer toxic side effects. Additionally, the use of minute amounts of drugs can lead to cost savings. In addition, nanotechnology is effectively applied in the preparation of such drugs as they are in nm sizes, considered one of the earliest cutoff values for the production of products utilized in nanotechnology. Early concepts described gold nanoshells as one of the successful therapies for cancer and associated diseases where the benefits of nanomedicine include effective active or passive targeting. Common medicines are degraded at a higher rate, whereas the degradation of macromolecules is time-consuming. All of the discussed properties are responsible for executing the physiological behaviors occurring at the following scale, depending on the geometry. Finally, large nanomaterials based on organic, lipid, inorganic, protein, and synthetic polymers have also been utilized to develop novel cancer cures.

Mechanistic insight of DACH1 receptor in the development of carcinoma insurgence through MD simulation studies.

Proteins are key player in the prognosis and therapeutics of carcinomas through the interactions of downstream signalling cascades. Current work insight the structural and mutational analysis of DACH1 in association with carcinogenesis. The homology modelling was employed to predict mutant and wild protein models and their reliability and accuracy was verified through multiple online approaches. Furthermore, MD simulation technique was employed to check the mutation effects on the stability of DACH1 through root mean square deviation and fluctuation graphs. Our results proposed that DACH1 mutation (C188Y) may cause lethal effects and can disturb the DACH1 structure. The observed mutational results showed that C188Y may cause some lethal effect in human body. Based on aforementioned computational assessments, it has concluded that DACH1 could be used as good therapeutic target in the prognosis and therapeutic of carcinoma insurgence.Communicated by Ramaswamy H. Sarma.

Antibiogram and molecular characterization of multi-drug resistant microorganisms isolated from urinary tract infections.

Bacteria are the commonest etiological factor among the microbes that cause UTIs. The most prevalent bacteria identified in the lab are Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa. Antibiotics are the empiric therapy for such infections but the reoccurrence rate is becoming high owing to the development of resistance due to their irrational and indiscriminate use across the globe. This study was designed on UTI cases of OPD, Medical, Nephrology, Surgical, Main OT, Urology and ICU wards of Allied hospital Faisalabad. 11 antibiotics were used which showed that E. coli is sensitive to Amikacin, Gentamicin, Imipenem, Piperacillin tazobactam, and Polymyxin B. Klebsiella pneumonia showed sensitivity for Amikacin, Gentamicin, Nitrofurantoin, Imipenem, Polymyxin B, Piperacillin tazobactam and Trimethoprim-sulfamethoxazole. While Pseudomonas aurignosa showed resistance to Amikacin, Ciprofloxacin, Gentamicin, Piperacillin tazobactam, Imipenem, and Polymyxin B. E. coli exhibited the highest sensitivity for Piperacillin tazobactam, Klebsiella pneumonia for Imipenem and Pseudomonas aurignosa for Ciprofloxacin. Further, the isolated DNA samples of these microorganisms were confirmed by gel electrophoresis and subjected to molecular characterization by performing trace file and phylogenetic tree analysis.

Linear Cryogel Arrays: On the Fast Track for Borreliosis Detection.

The detection of IgG/IgM antibodies is a crucial tool for the diagnosis of infectious diseases as they give specific information such as the stage of infection or when it approximately occurred. In this work, a linear cryogel array (LCA) technology is described for the detection of IgG and IgM antibodies, indicative of a borreliosis infection in human sera. The LCA consists of a transparent capillary filled with functionalized cryogel compartments. For the generation of these cryogel arrays, solutions containing a photo-copolymer and the appropriate antigens are sucked into a surface-modified glass capillary. The solution compartments are separated from each other through air pockets. After freezing the solutions, a photo-induced cross-linking process is performed, through which the solutions are transformed into cryogel compartments, covalently attached to the capillary walls. We show that the LCA technology allows the simultaneous detection of IgG and IgM antibodies via a sandwich immunoassay in sera from Borrelia-infected patients within 1 h for sample sizes of only 12 µL. A study with sera from 42 patients conducted with the LCAs and referenced - depending on the source of the sera - to a commercial line immunoassay and a chemiluminescent immunoassay, which are currently widely used for Lyme disease screening, demonstrates the diagnostic potential of the approach.

Phytochemical analysis and protective effects of Vaccinium macrocarpon (cranberry) in rats (Rattus norvegicus) following ethylene oxide-induced oxidative insult.

The Vaccinium genus comprises more than 126 genera of perennial flowering plants that are commonly adapted to poor and acidic soils or epiphytic environments. Their molecular and genomic characterization is a result of the recent advent in next-generation sequencing technology. In the current research, extracts were prepared in different media, such as petroleum ether, methanol and ethanol. An extract of Vaccinium macrocarpon (cranberry) was used at a dose of 200-400 mg/kg by weight (B.wt). Levels of oxidative stress markers, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), advanced oxidation protein products (AOPPs) and malondialdehyde (MDA), were measured. A histopathological study of six vital organs in rats was also conducted. The results indicated that the antioxidant levels were lower in the group given only ethylene oxide (EtO) but higher in the groups receiving cranberry extract as a treatment. Major improvements were also observed in stress markers such as advanced oxidation protein products (AOPPs) and MDA following cranberry treatment. Histopathological changes induced by EtO were observed in the heart, kidney, liver, lung, stomach and testis and were reversed following cranberry treatment. The major toxic effects of EtO were oxidative stress and organ degeneration, as observed from various stress markers and histopathological changes. Our study showed that this extract contains strong antioxidant properties, which may contribute to the amelioration of the observed toxic effects.

Extensive drug-resistance in strains of Escherichia coli and Klebsiella pneumoniae isolated from paediatric urinary tract infections.

OBJECTIVES: Urinary tract infections (UTIs) in children are rapidly increasing worldwide and are commonly caused by extensively drug-resistant bacteria. This study determines the prevalence of UTIs in paediatric patients and evaluates the pattern of extensively drug-resistance in Escherichia coli and Klebsiella pneumoniae strains isolated from paediatric UTI patients. METHODS: Uropathogenic bacterial strains were isolated from paediatric patients with UTIs admitted to the Institute of Child Health, Lahore, Pakistan. Strains of both E. coli and K. pneumoniae were identified using biochemical characterisation and subjected to antibiotic susceptibility assays for 21 common antimicrobial drugs in order to determine their extensively drug-resistant profile. RESULTS: We isolated 63 E. coli and 37 K. pneumoniae strains from 130 paediatric patients with UTIs over a period of six months. The antibiotic susceptibility assays showed that both the E. coli and K. pneumoniae strains exhibited a high degree of resistance against co-amoxiclav, cefuroxime, cefixime, cefotaxime, ceftazidime, ceftriaxone, ciprofloxacin, nalidixic acid, norfloxacin, pepedemic acid, and co-trimoxazole. However, several of the antimicrobial agents, including polymyxin B, colistin sulphate, chloramphenicol, nitrofurantoin, and fosfomycin, were found to retain their antimicrobial activities against both pathogens. The five highest antibiotic resistant strains were identified as E. coli strains ZK9, ZK40, and ZK60 and K. pneumoniae ZK32 and ZK89 using 16S rRNA gene sequencing. CONCLUSION: Our study demonstrates that E. coli and K. pneumonia are the dominant extensively drug-resistant uropathogenic bacteria in community-acquired UTIs in our cohort. These uropathogens were found to be resistant to the majority of the routinely-used classes of ß-lactams, pyridopyrimidines, quinolones, and fluoroquinolone antibiotics, and these findings may be useful for clinicians in their treatment of paediatric UTIs.

Freeze-drying improves DNA yield from teeth.

The common method of preparing teeth prior to DNA extraction involves cleaning, decontamination, drying and pulverisation. Moisture in post-mortem teeth can promote bacterial growth and hydrolytic damage that could contribute to DNA degradation, whilst also possibly reducing the efficiency of sample pulverisation and DNA release. Here we compared DNA extraction from pig teeth, with- and without freeze-drying, to examine the impact of removing moisture on DNA yield. Quantitative real-time polymerase chain reaction (qPCR) was used to quantify an 83 bp mitochondrial DNA fragment and two nuclear DNA fragments of 82 bp and 150 bp. The comparative results showed that sample preparation with freeze-drying resulted in a higher DNA yield without compromising the DNA quality. This study highlights the advantage of incorporating a freeze-drying to improve the DNA yield and minimising the loss of DNA during sample preparation of teeth.

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.

Inhibitory Potential of Phytochemicals on Interleukin-6-Mediated T-Cell Reduction in COVID-19 Patients: A Computational Approach.

BACKGROUND: A recent COVID-19 pandemic has resulted in a large death toll rate globally and even no cure or vaccine has been successfully employed to combat this disease. Patients have been reported with multi-organ dysfunction along with acute respiratory distress syndrome which implies a critical situation for patients and made them difficult to breathe and survive. Moreover, pathology of COVID-19 is also related to cytokine storm which indicates the elevated levels of interleukin (IL)-1, IL-6, IL-12, and IL-18 along with tumor necrosis factor (TNF)-α. Among them, the proinflammatory cytokine IL-6 has been reported to be induced via binding of severe acute respiratory syndrome coronavirus 2 (SARS)-CoV-2 to the host receptors. METHODOLOGY: Interleukin-6 blockade has been proposed to constitute novel therapeutics against COVID-19. Thus, in this study, 15 phytocompounds with known antiviral activity have been subjected to test for their inhibitory effect on IL-6. Based on the affinity prediction, top 3 compounds (isoorientin, lupeol, and andrographolide) with best scores were selected for 50 ns molecular dynamics simulation and MMGB/PBSA binding free energy analysis. RESULTS: Three phytocompounds including isoorientin, lupeol, and andrographolide have shown strong interactions with the targeted protein IL-6 with least binding energies (-7.1 to -7.7 kcal/mol). Drug-likeness and ADMET profiles of prioritized phytocompounds are also very prominsing and can be further tested to be potential IL-6 blockers and thus benficial for COVID-19 treatment. The moelcular dynamics simulation couple with MMGB/PBSA binding free energy estimation validated conformational stability of the ligands and stronger intermolecular binding. The mean RMSD of the complexes is as: IL6-isoorientin complex (3.97 Å ± 0.77), IL6-lupeol (3.97 Å ± 0.76), and IL6-andrographolide complex (3.96 Å ± 0.77). In addition, the stability observation was affirmed by compounds mean RMSD: isoorientin (0.72 Å ± 0.32), lupeol (mean 0.38 Å ± 0.08), and andrographolide (1.09 Å ± 0.49). A similar strong agreement on systems stability was unraveled by MMGB/PBSA that found net binding net ~ -20 kcal/mol for the complexes dominated by van der Waal interaction energy. CONCLUSION: It has been predicted that proposing potential IL-6 inhibitors with less side effects can help critical COVID-19 patients because it may control the cytokine storm, a major responsible factor of its pathogenesis. In this study, 3 potential phytocompounds have been proposed to have inhibitory effect on IL-6 that can be tested as potential therapeutic options against SARS-CoV-2.

Role of Oxidative Stress and the Identification of Biomarkers Associated With Thyroid Dysfunction in Schizophrenics.

Background: Schizophrenia is associated with a deficiency of dietary antioxidants like vitamin B6, B9, and B12 resulting in defective methylation leading to hyperhomocysteinemia. Hyperhomocysteinemia causes mitochondrial DNA damage, oxidative stress, vascular damage, and lipid peroxidation. Oxidative stress and increase in reactive oxygen species result in 8-oxodG production which induces apoptosis of both astrocytes and thyrocytes thus predisposing them to thyroid dysfunction and neurodegeneration. Furthermore, the presence of excessive free radicals increases thyroid thermogenesis causing hyperthyroidism or its excess may cause hypothyroidism by inhibiting iodide uptake. In the present study, we evaluated the various biomarkers associated with thyroid dysfunction in schizophrenics. Materials and Methods: 288 patients suffering from schizophrenia and 100 control subjects were screened for liver function tests (LFTs) such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). Also, the stress markers, namely malondialdehyde (MDA), homocysteine, cysteine, methionine, the thyroid profile including triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), thyroxine peroxide antibody (TPO-Ab); TSH receptor-Ab (TSHr-Ab), dietary antioxidants, lipids, cytokines, aminoacids and hormones, vitamins and trace elements, and other biochemical parameters. Results: The LFTs showed elevated levels of ALT (45.57 ± 4.87 Vs. 26.41 ± 3.76 U/L), AST (40.55 ± 1.34 Vs. 21.92 ± 3.65 U/L), ALP (121.54 ± 4.87 Vs. 83.76 ± 5.87 U/L), and total bilirubin (2.63 ± 0.987 Vs. 1.10 ± 0.056 mg/dl), in schizophrenics than controls. Increased levels of MDA (3.71 ± 0.967 Vs. 1.68 ± 0.099) and homocysteine (17.56 ± 2.612 Vs. 6.96 ± 1.987 µmol/L were observed in schizophrenics compared to the controls, indicating increased stress. Levels of cysteine and methionine were decreased in schizophrenics than the controls (1.08 ± 0.089 Vs. 4.87 ± .924 µmol/L and 17.87 ± 1.23 Vs. 99.20 ± 5.36 µmol/L). The levels of TPO-Ab (IU/ml), Tg-Ab (pmol/L), and TSHr-Ab (IU/L) were observed to be higher in the patients' group as compared to control subjects (9.84 ± 2.56 Vs. 5.81 ± 1.98, 55.50 ± 2.98 Vs. 32.95 ± 2.87 and 2.95 ± 0.0045 Vs. 1.44 ± 0.0023 respectively). Levels of Vitamin B6, B9, and B12 were also significantly decreased in the patients compared to the healthy controls. Conclusion: The schizophrenics, demonstrated altered liver function, increased stress markers, and decreased dietary antioxidants. Reduced primary and secondary antioxidant levels, may result in hyperhomocysteinemia and cause further DNA and mitochondrial damage. Therefore, homocysteine and/or prolactin levels may serve as candidate prognostic markers for schizophrenia. Also, both neurological symptoms and the susceptibility to thyroid disorders may be prevented in the initial stages of this debilitating disorder by appropriate dietary supplementation of antioxidants which can rectify a reduction in primary and secondary antioxidants, and disturbed prolactin-serotonin-dopamine interactions in schizophrenics.