In silico exploration of PD-L1 binding compounds: Structure-based virtual screening, molecular docking, and MD simulation.

Programmed death-ligand 1 (PD-L1), a transmembrane protein, is associated with the regulation of immune system. It frequently has overexpression in various cancers, allowing tumor cells to avoid immune detection. PD-L1 inhibition has risen as a potential strategy in the field of therapeutic immunology for cancer. In the current study, structure-based virtual screening of drug libraries was conducted and then the screened hits were docked to the active residues of PD-L1 to select the optimal binding poses. The top ten compounds with binding affinities ranging from -10.734 to -10.398 kcal/mol were selected for further analysis. The ADMET analysis of selected compounds showed the compounds meet the criteria of ADMET properties. Further, the conformational changes and binding stability of the top two compounds was analyzed by conducting 200 ns simulation and it was observed that the hits did not exert conformational changes to the protein structure. All the results suggest that the chosen hits can be considered as lead compounds for the inhibition of biological activity of PD-L1 in in vitro studies.

Association analysis of miRNA-146a and miRNA-196a polymorphism with breast cancer risk in Khyber Pakhtunkhwa, Pakistan: a preliminary study.

BACKGROUND: microRNAs (miRNAs) are small, noncoding RNA molecules, functioning either as oncogenes or tumor suppressor genes. SNPs in miRNAs might modify the expression of genes associated with miRNAs, enhancing susceptibility to breast cancer. Both miRNA-146a (rs2910164) and miRNA-196a (rs11614913) are identified and significantly associated with breast cancer risk in several ethnicities, but remains unexplored in Khyber Pakhtunkhwa population of Pakistan. METHODS: This study was aimed to check the relation of selected SNPs with breast cancer risk. The research cohort included 100 breast cancer patients and 100 healthy controls. All the participants were subjected for DNA extraction followed by T-ARMS PCR and gel electrophoresis. RESULTS: The results revealed a strong association between risk allele (G) of miRNA-146a and increased risk of breast cancer (OR = 2.04, P = 0.0006). Similarly, heterozygous and mutant genotypes also indicated high risk and significant association with breast cancer risk (CG; OR = 0.51, 9 P = 0.0001) (GG; OR = 3.76, P = 0.04). However, risk allele (T) of miRNA-196a (rs11614913) failed to exhibit significant association with breast cancer risk (OR = 0.92 P = 0.68). Similarly, the heterozygous and mutant genotype did not show significant association with breast cancer risk (CT; OR = 0.52, P = 0.125 (TT; OR = 0.88, P = 0.84). Furthermore, miRNA-146a (rs2910164) and miRNA-196a (rs11614913) polymorphisms exhibited non-significant associations with family history (P = 0.34, P = 0.77), PR status (P = 0.310, P = 0.397), ER status (P = 0.992, P = 0.981), nodal status (P = 0.86, P = 0.90), and menstrual status (P = 0.97, P = 0.09). Notably, miRNA-196a showed a significant association with the metastasis group (P = 0.010) and cancer stages (P = 0.047). CONCLUSIONS: In conclusion, this study highlights the association of miRNA-146a (rs2910164) polymorphism with breast cancer risk but suggested non-significant association of miRNA-196a (rs11614913) with breast cancer risk. However, these findings need to be confirmed through larger data set for more accurate result.

Significant Association of Candidate Genes (AGTR1 and TGF-Β1) Polymorphism with Diabetic Nephropathy in Diabetes Mellitus Type 2 Patients.

BACKGROUND/AIMS: Diabetic nephropathy (DN) is one of the complications of diabetes mellitus (DM). This study aimed to investigate the association between genetic polymorphisms, specifically AGTR1 (rs5186) and TGF-ß1 (rs1800470), and the risk of developing Diabetic nephropathy (DN) in type 2 diabetes mellitus patients, compared to those without DN and healthy controls. METHODS: A case-control study was conducted on 165 diabetic patients (59 with diabetic nephropathy (DN) and 54 without DN (DM)), and 52 healthy controls (HC). The genotyping was done using amplification refractory mutation system method (ARMS-PCR). Age, gender, and duration of diabetes were matched across groups. Clinical parameters including FBS, RBS, HbA1C, creatinine, urea, SBP, DBP, total cholesterol, triglycerides, LDL, and BMI were assessed. RESULTS: Diabetic patients with nephropathy exhibited significantly higher levels of clinical parameters compared to those without nephropathy and healthy controls. The risk allele of AGTR1 , C (p <0.0001), and risk allele containing genotypes AC (p <0.0001) and CC (p - 0.0010) were significantly higher in DN patients compared to DM and HC groups. Similarly, the TGF-ß1 risk allele C (p - 0.0001), and corresponding genotypes TC (p - 0.0038) and CC (p - 0.0027) were significantly associated with increased risk of diabetic nephropathy compared to DM and HC groups. CONCLUSION: The data showed significant association of AGTR1 (rs5186) and TGF-ß1 (rs1800470) polymorphism with an increased risk of diabetic nephropathy in type 2 diabetes mellitus patients. More investigation will be required to disseminate the results, while increasing the samples size and using whole genome sequencing.

In silico design of peptide inhibitors for Dengue virus to treat Dengue virus-associated infections.

Dengue virus is a single positive-strand RNA virus that is composed of three structural proteins including capsid, envelope, and precursor membrane while seven non-structural proteins (NS1, NS2A, NS2B, NS3A, NS3B, NS4, and NS5). Dengue is a viral infection caused by the dengue virus (DENV). DENV infections are asymptomatic or produce only mild illness. However, DENV can occasionally cause more severe cases and even death. There is no specific treatment for dengue virus infections. Therapeutic peptides have several important advantages over proteins or antibodies: they are small in size, easy to synthesize, and have the ability to penetrate the cell membranes. They also have high activity, specificity, affinity, and less toxicity. Based on the known peptide inhibitor, the current study designs peptide inhibitors for dengue virus envelope protein using an alanine and residue scanning technique. By replacing I21 with Q21, L14 with H14, and V28 with K28, the binding affinity of the peptide inhibitors was increased. The newly designed peptide inhibitors with single residue mutation improved the binding affinity of the peptide inhibitors. The inhibitory capability of the new promising peptide inhibitors was further confirmed by the utilization of MD simulation and free binding energy calculations. The molecular dynamics simulation demonstrated that the newly engineered peptide inhibitors exhibited greater stability compared to the wild-type peptide inhibitors. According to the binding free energies MM(GB)SA of these developed peptides, the first peptide inhibitor was the most effective against the dengue virus envelope protein. All peptide derivatives had higher binding affinities for the envelope protein and have the potential to treat dengue virus-associated infections. In this study, new peptide inhibitors were developed for the dengue virus envelope protein based on the already reported peptide inhibitor.

Development and characterization of a biodegradable film based on guar gum-gelatin@sodium alginate for a sustainable environment.

A significant amount of plastic trash has been dumped into the environment across the world, contributing to the present white pollution crisis. Therefore, plastic manufacturing and disposal must be examined. Biodegradable plastics (BPs) have recently become the subject of study due to their beneficial biodegradability and harmlessness, and they have been the most efficient method for addressing the issue of plastic pollution. This study aims to enhance the synthesis of biodegradable polymers from sodium alginate (Na-Alg) with the addition of guar gum, corn starch, and gelatin using the solution-casting method, followed by mixing in suitable proportions and drying at a certain temperature, resulting in thin film formation. To enhance qualities of the already produced polymer, additional substances such as glycerol, PVA, and latex were added as plasticizers. Characterization techniques such as scanning electron microscopy (SEM), tensile strength, thermogravimetric analysis (TGA), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), differential scanning calorimetry (DSC), UV-vis spectroscopy, and Fourier transform infrared (FTIR) spectroscopy were used to study structural characteristics, surface morphology, polymeric linkages, water absorption capabilities, chemical conductivity, and light transmittance of the newly formed films. These characterization results depict a remarkable achievement in the sense of the high degradability and impressive tensile strength of the newly formed films. In addition, SEM images indicated a porous structure with interconnected pores. FT-IR confirms the occurrence of molecular interactions between separate components. Consequently, different films showed different behavior of degradability, and it is suggested from interpreting the results that the polymeric films may be a viable biodegradable option.

Amelioration of tableting properties and dissolution rate of naproxen co-grinded with nicotinamide: preparation and characterization of co-grinded mixture.

OBJECTIVE AND SIGNIFICANCE: Reducing the dimensions, when other additives are present, shows potential as a method to improve the dissolution and solubility of biopharmaceutical classification system class II drugs that have poor solubility. In this investigation, the process involved grinding naproxen with nicotinamide with the aim of improving solubility and the rate of dissolution. METHODS: Naproxen was subjected to co-milling with urea, dimethylurea, and nicotinamide using a planetary ball mill for a duration of 90 min, maintaining a 1:1 molar ratio for the excipients (screening studies). The co-milled combinations, naproxen in its pure milled form, and a physical mixture were subjected to analysis using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), and solubility assessment. The mixture displaying the highest solubility (naproxen-nicotinamide) was chosen for further investigation, involving testing for intrinsic dissolution rate (IDR) and Fourier-transform infrared spectroscopy (FTIR) after co-milling for both 90 and 480 min. RESULTS AND CONCLUSION: The co-milled combination, denoted as S-3b and consisting of the most substantial ratio of nicotinamide to naproxen at 1:3, subjected to 480 min of milling, exhibited a remarkable 45-fold increase in solubility and a 9-fold increase in IDR. XRPD analysis of the co-milled samples demonstrated no amorphization, while SEM images portrayed the aggregates of naproxen with nicotinamide. FTIR outcomes negate the presence of any chemical interactions between the components. The co-milled sample exhibiting the highest solubility and IDR was used to create a tablet, which was then subjected to comprehensive evaluation for standard attributes. The results revealed improved compressibility and dissolution properties.

Chemometric Analysis and Human Health Implications of Trace and Heavy/Non-Essential Metals through ingestion of Carbonated and Non-Carbonated Beverages.

Elevated levels of trace metals (TMs) and heavy/non-essential metals (HnMs) in commonly consumed beverages concern the public and regulatory agencies. Thus, frequent monitoring of these metals is critically important. The present study intended to assess TMs and HnMs concentrations and associated health risks in beverages. Ten metals, such as Mn, Co, Cr, Cu, and Zn (TMs) and Ni, Cd, Pb, Al, and As (HnMs), were quantified in different beverage brands categorized into two groups such as non-carbonated and carbonated beverages. Chemometric analysis such as hierarchical cluster analysis (HCA), Pearson's correlation coefficient (PCC), and principal component analysis (PCA) were also performed to demonstrate the possible natural and anthropogenic sources of metal contamination. Among the TMs, the mean concentration of Zn (233.3 ± 3.3-291.7 ± 3.2 µg/L) followed by Mn (119.0 ± 2.3-146.4 ± 2.2 µg/L) was found highest in both carbonated and non-carbonated beverage samples. In the case of HnMs, the lowest mean concentration of Cd (7.4 ± 0.9-18.6 ± 1.2 µg/L) followed by Pb (4.1 ± 0.4-4.5 ± 0.4 µg/L) was observed in both types of beverage samples. The tolerable dietary intake (TDI) value for Ni and provisional tolerable monthly intake (PTMI) value for Cd were higher than the value established by the WHO and EFSA. The computed values of the hazard index (HI < 1) and the cumulative cancer risk (CCR) indicated a low risk of exposure.

Managing energy transition alongside environmental protection by making use of AI-led butanol powered SI engine optimization in compliance with SDGs.

Enormous consumption of fossil fuel resources has risked energy accessibility in the upcoming years. The price fluctuation and depletion rate of fossil fuels instigate the urgent need for searching their reliable substitute. The current study tries to address these issues by presenting butanol as a replacement for gasoline in SI engines at various speeds and loading conditions. The emission and performance parameters were ascertained for eight distinct butanol-gasoline fuel blends. The oxygenated butanol substantially increases engine efficiency and boosts power with lower fuel consumption. The carbon emissions were also observed to be lower in comparison with gasoline. Furthermore, the Artificial Intelligence (AI) approach was used in predicting engine performance running on the butanol blends. The correlation coefficients for the data training, validation, and testing were found to be 0.99986, 0.99942, and 0.99872, respectively. It was confirmed that the ANN predicted results were in accordance with the established statistical criteria. ANN was paired with Response Surface Methodology (RSM) technique to comprehend the influence of the sole design parameters along with their statistical interactions controlling the responses. Similarly, the R2 value of responses in case of RSM were close to unity and mean relative errors (MRE) were confined under specified range. A comparative study between ANN and RSM models unveiled that the ANN model should be preferred. Therefore, a joint utilization of the RSM and ANN can be more effective for reliable statistical interactions and predictions.

Psychiatric implications of anti-seizure medications in epileptic population.

BACKGROUND AND OBJECTIVE: Epilepsy is a prevalent neurological disorder that affects a significant number of individuals globally. This condition is associated with a high occurrence of psychiatric comorbidities, which can significantly affect the quality of life of individuals affected. The aim of this study was to investigate the association between antiseizure therapies and the likelihood of psychiatric comorbidities in individuals with epilepsy. METHODOLOGY: Data for this study was gathered from the Neurology referral center in Islamabad, Pakistan. A standardized questionnaire was utilized to gather data from 120 individuals diagnosed with epilepsy. The survey consisted of inquiries regarding the management of seizures, the utilization of anti-seizure medications, and the presence of psychiatric comorbidities. The data was analyzed using the Statistical Package for the Social Sciences (SPSS). RESULTS: The findings indicated that individuals who were using multiple antiseizure medications had a notably higher likelihood of having psychiatric comorbidities in comparison to those who were on mono therapy (p = 0.010). suggests that patients with unsuccessful seizure control are more probable to have psychiatric comorbidities as compared to those with good seizure control (p = 0.029). CONCLUSION: To conclude poor seizure control and poly therapy are associated with increased risk of psychiatric comorbidities.

Design and synthesis of novel dihydropyridine- and benzylideneimine-based tyrosinase inhibitors.

Tyrosinase (TYR) inhibitors are very significant as they inhibit enzyme tyrosinase activity, and its inhibition is vital for skin care, anticancer medication, and antibrowning of fruits and vegetables. This work presents a novel and economical route for the preparation of new synthetic tyrosinase inhibitors using amlodipine (4). The novel conjugates 6 (a-o) were designed, synthesized, and characterized by spectroscopic analyses, including Fourier transform infrared and low- and high-resolution mass spectroscopy. The purified compound 4 was refluxed with various aldehydes and ketones 5 (a-o) for 5-8 h in methanol at 60°C-90°C. This research modified the drug in a step-by-step manner to develop therapeutic properties as a tyrosinase inhibitor. The structures of synthesized ligands 6 (a-o) were established based on spectral and analytical data. The synthesized compounds 6 (a-o) were screened against tyrosinase enzyme. Kojic acid was taken as standard. All the prepared compounds 6 (a-o) have good inhibition potential against the enzyme tyrosinase. Compounds 6o, 6b, 6f, and 6k depicted excellent antityrosinase activity. Compound 6k, with an IC50 value of 5.34 ± 0.58 µM, is as potent as the standard kojic acid (IC50 6.04 ± 0.11 µM), standing out among all synthesized compounds 6 (a-o). The in silico studies of the conjugates 6 (a-o) were evaluated via PatchDock. Compound 6k showed a binding affinity score of 8,999 and an atomic contact energy (ACE) value of -219.66 kcal/mol. The structure-activity relationship illustrated that the presence of dihydropyridine nuclei and some activating groups at the ortho and para positions of the benzylideneimine moiety is the main factor for good tyrosinase activity. The compound 6k could be used as a lead compound for drug modification as a tyrosinase inhibitor for skin care, anticancer medication, and antibrowning for fruits and vegetables.

BRAF and RET polymorphism association with thyroid cancer risk, a preliminary study from Khyber Pakhtunkhwa population.

BACKGROUND: Thyroid cancer, originating in the neck's thyroid gland, encompasses various types. Genetic mutations, particularly in BRAF and RET genes are crucial in its development. This study investigates the association between BRAF (rs113488022) and RET (rs77709286) polymorphisms and thyroid cancer risk in the Khyber Pakhtunkhwa (KP) population. METHODS: Blood samples from 100 thyroid cancer patients and 100 healthy controls were genotyped using ARMS-PCR followed by gel electrophoresis and statistical analysis. RESULTS: Analysis revealed a significant association between the minor allele T of BRAF (rs113488022) and thyroid cancer risk (P = 0.0001). Both genotypes of BRAF (rs113488022) showed significant associations with thyroid cancer risk (AT; P = 0.0012 and TT; P = 0.045). Conversely, the minor allele G of RET (rs77709286) exhibited a non-significant association with thyroid cancer risk (P = 0.2614), and neither genotype showed significant associations (CG; P = 0.317, GG; P = 0.651). Demographic and clinical parameters analysis using SPSS showed a non-significant association between BRAF and RET variants and age group (P = 0.878 and P = 0.536), gender (P = 0.587 and P = 0.21), tumor size (P = 0.796 and P = 0.765), or tumor localization (P = 0.689 and P = 0.727). CONCLUSION: In conclusion, this study emphasizes the significant association between BRAF polymorphism and thyroid cancer risk, while RET polymorphism showed a less pronounced impact. Further validation using larger and specific datasets is essential to establish conclusive results.

BRCA2 Polymorphisms and Breast Cancer Susceptibility: a Multi-Tools Bioinformatics Approach.

BACKGROUND/AIMS: The main focus of this investigation is to identify deleterious single nucleotide polymorphisms (SNPs) located in the BRCA2 gene through in silico approach, thereby,providing an understanding of potential consequences regarding the susceptibility to breast cancer. METHODS: The GenomAD database was used to identify SNPs. To determine the potential adverse consequences, our study employed various prediction tools, including SIFT, PolyPhen, PredictSNP, SNAP2, PhD-SNP, and ClinVar. The pathogenicity associated with the deleterious snSNPs was evaluated bu MutPred and Fathmm. Additionally, I-Mutant and MuPro were used to assess the stability, followed by conservation and protein-protein interaction analysis using robust computational tools. The 3D structure of BRCA2 protein was generated by SwissModel, followed by validation using PROCHECK and Errat. RESULTS: The GenomAD database was used to identify a total of 7, 921 SNPs, including 1940 missense SNPs. A set of 69 SNPs predicted by consensus to be damaging across all platforms was identified. Mutpred and Fathmm identified 48 and 38 SNPs, respectively to be associated with cancer. While I- Mutant and MuPro assays suggested 22 SNPs to decrease protein stability. Additionally, these 22 SNPs reside within highly conserved regions of the BRCA2 protein. Domain analysis, utilizing InterPro, pinpointed 18 deleterious mutations within crucial DNA binding domains and one in the BRC repeat region. CONCLUSION: This study establishes a foundation for future experimental validations and the creation of breast cancer-targeted treatment approaches.

Molecular characterization of plasma virome of hepatocellular carcinoma (HCC) patients.

Hepatocellular carcinoma (HCC) stands as the most common cancer type, arising from various causes, and responsible for a substantial number of cancer-related fatalities. Recent advancements in viral metagenomics have empowered scientists to delve into the intricate diversity of the virosphere, viral evolution, interactions between viruses and their hosts, and the identification of viral causes behind disease outbreaks, the development of specific symptoms, and their potential role in altering the host's physiology. The present study had the objective of "Molecular Characterization of HBV, HCV, anelloviruses, CMV, SENV-D, SENV-H, HEV, and HPV viruses among individuals suffering from HCC." A total of 381 HCC patients contributed 10 cc of blood each for this study. The research encompassed the assessment of tumor markers, followed by molecular characterization of HBV, HCV, Anelloviruses (TTV, TTMV, and TTMDV), SENV-H and SENV-D viruses, HEV, CMV, and HPV, as well as histopathological examinations. The outcomes of this study revealed that majority of the HCC patients 72.4% (276/381) were male as compared to females. HCV infection, at 76.4% (291 out of 381), exhibited a significant association (p < 0.05) with HCC. Most patients displayed singular lesions in the liver, with Child Pugh Score Type B being the predominant finding in 45.2% of cases. Plasma virome analysis indicated the prevalence of TTMDV (75%), followed by TTMV (70%) and TTV (42.1%) among anelloviruses in HCC patients. Similarly, SENV-H (52%) was followed by SENV-D (20%), with co-infections at 15%. The presence of CMV and HEV among the HCC patients was recorded 5% each however 3.5% of the patients showed the presence of HPV. In conclusion, this study underscores that HCC patients serve as reservoirs for various pathogenic and non-pathogenic viruses, potentially contributing to the development, progression, and severity of the disease.

Fractional analysis of non-linear fuzzy partial differential equations by using a direct procedure.

In this study, an accurate analytical solution is presented for fuzzy FPDEs. It is done by using a novel method called the Laplace-residual power series (LRPSM) to build a series solution to the given problems. The fundamental instruments of the employed method are the Laplace transform, fractional Laurent, and fractional power series. Using the idea of a limit at infinity, we provide a series solution to a fuzzy FPDE with quick convergence and simple coefficient finding. We analyze three cases to obtain approximate and exact solutions to show the effectiveness and reliability of the Laplace- residual power series approach. To demonstrate the accuracy of the suggested procedure, we compare the findings to the real data.

Nanocellulose/wood ash-reinforced starch-chitosan hydrogel composites for soil conditioning and their impact on pea plant growth.

Hydrogels are 3-dimensional polymer networks capable of absorbing a large amount of water. Natural polymeric hydrogels are biodegradable, non-toxic and biocompatible. They can effectively retain nutrients for the plant and can be used as soil conditioners. This study uses a chemical cross-linking technique to synthesize starch and chitosan-based hydrogel using citric acid as a cross-linker. Additionally, hydrogel composites were developed by incorporating wood ash, nano-cellulose, and NPK (nitrogen-phosphorus-potassium) fertilizer as fillers to enhance their properties. The formulated hydrogel/hydrogel composite samples were characterized by FTIR spectroscopy, SEM analysis, X-ray diffraction and thermo-gravimetric analysis. The experiment results showed the chemical cross-linking among the polymeric chain and the semi-crystalline nature of the hydrogel/hydrogel composite samples. The swelling capacity of the hydrogel/hydrogel composite samples was 200-420% (in distilled water) and 104-220% (in saline medium) and demonstrated biodegradability within 110 days. The NPK reinforced hydrogel composite showed an excellent effect on the growth of pea plants (leaves count = 37, stem height = 20.2 cm), and could be effectively used as soil conditioners for agricultural applications. Considering the ability of hydrogel composites to reduce irrigation needs, enhance nutrient retention, and improve crop production, these novel hydrogel composites present an economically viable solution for sustainable agricultural practices.

Exploring the Differential Effects of Transcranial Direct Current Stimulation: A Comparative Analysis of Motor Cortex and Cerebellar Stimulation.

Background: Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation technique. Constant electric current is passed through the patient's scalp with the aim of modulating cortical excitability. Stroke is a cerebrovascular disease characterized by hemorrhage or cerebral ischemia. This systematic review and meta-analysis are aimed at comparing the efficacy of motor cortex stimulation with that of cerebellar stimulation by using transcranial direct current stimulation. Method: Google Scholar, PubMed, EMBASE, Cochrane CENTRAL, and Physiotherapy Evidence Database (Pedro) databases were searched for studies. The extracted qualitative data was synthesized systematically. Cochrane RevMan software was used to conduct a meta-analysis of quantitative data. The fixed effects mean difference of the collected data was calculated at a 95% confidence interval (CI) for the changes in balance and side effects. Results: This research included 10 articles with seven studies assessing changes in balance (outcome measured in CoP and FMA scores) and side effects (tingling and itching were the most prevalent). There was no significant difference between the efficacy levels of m1-tDCS versus ctDCS (P = 0.18), m1-tDCS versus sham (P = 0.92), and ctDCS versus sham (P = 0.19). Itching and tingling sensation were the most common and were significantly prevalent in sham interventions (P < 0.00001). Conclusion: We found that motor cortex and cerebellar stimulations are both effective in improving motor function in stroke patients. There are no adverse effects to using the interventions besides mild itching and tingling experienced during the stimulation.

Development of Plumeria alba extract supplemented biodegradable films containing chitosan and cellulose derived from bagasse and corn cob waste for antimicrobial food packaging.

With the increase in global plastic pollution due to conventional plastic packaging (petroleum-derived), bioplastics have emerged as an alternative green source for practising a circular economy. This research aimed to extract cellulose from bagasse and corn cob waste and utilized in mixed form to prepare bioplastic film. The mixed cellulose was further reinforced with natural substances such as chitosan, bentonite, and P. alba extract. These newly developed bioplastics films were characterized by various physical tests like film thickness, moisture content, water solubility and spectroscopic techniques such as Fourier transform infrared (FTIR), scanning electron microscopy-energy dispersive spectroscopic (SEM-EDX), thermal gravimetric analysis (TGA), and ultraviolet-visible (UV-Vis) spectroscopy for opacity testing. The results revealed the enhanced bioplastic thermal and mechanical characteristics through robust interactions between cellulose and bentonite molecules. Moreover, incorporating chitosan solution as reinforcements in bio-composite films resulted in improved water barrier properties. The results indicated lower absorption in the UV range of 250-400 nm, attributed to the absence of UV-absorbing groups. Finally, their biodegradability was tested in soil, and 85.3 % weight loss of bioplastic films was observed after 50 days of the experiment which is the main task of this research. The antimicrobial properties of bioplastic films have been evaluated, and showed an inhibition zone of 16 mm against E. coli. After 12 days of incubation of sherbet berries, complete spoilage is identified in the control group compared to those covered with the bioplastic film. This outcome is attributed to the antioxidant and antimicrobial activities provided by chitosan and P. alba extract in the bioplastic film. The comprehensive outcomes of this study suggest the potential future adoption of these entirely bio-derived, environmentally sustainable and biodegradable bioplastic films as a viable substitute for the plastic packaging currently present in the market.

Human epidermal growth receptor polymorphisms (HER1-rs11543848 and HER2-rs1136201) exhibited significant association with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa, Pakistan.

Background and Aims: Breast cancer is the most common type of cancer in women. The genetic polymorphism in HER (HER1-rs11543848 and HER2-rs1136201) were found to be associated with breast cancer risk in different ethnicities worldwide with inconsistent results. The aim of this research study was to evaluate the association of HER1-rs11543848 and HER2-rs1136201 polymorphisms as a risk of breast cancer in Pashtun population of Khyber Pakhtunkhwa, Pakistan. Methods: A total of 314 women including 164 breast cancer patients and 150 age and gender-matched healthy controls were enrolled from June 2021 to May 2022. All the samples were subjected to DNA extraction followed by Tetra-ARMS-PCR for genotyping and gel electrophoresis. Results: Our results indicated that HER1-rs11543848 risk allele A (p = 0.0001) and heterozygous genotype GA (p = 0.0001) displayed highly significant association with breast cancer, while the homozygous mutant genotype AA indicated association but nonsignificant results (odds ratio [OR] = 2.637, 95% confidence interval [CI] = 1.2258-5.6756, p = 0.0833). Similarly, the HER2-rs1136201 risk allele G (p = 0.0023), the heterozygous genotype AG (p = 0.0530) and homozygous mutant genotype GG showed significant association (OR = 2.5946, 95% CI = 0.9876-6.8165, p = 0.0530) with breast cancer risk. Both the SNPs presented a higher but nonsignificant risk of breast cancer in postmenopausal women (OR = 2.242, p = 0.08 and OR = 2.009, p = 0.06). However, both the SNPs showed significant association (p < 0.005) with family history, metastasis, stage, luminal B, and TNBC. Conclusion: In conclusion, HER1-rs11543848 and HER2-rs1136201 polymorphisms are significantly associated with the higher risk of breast cancer in Pashtun population of Khyber Pakhtunkhwa, Pakistan. These findings advocate for further exploration with larger datasets, offering promising avenues for personalized approaches in breast cancer research and potentially enhancing clinical practices for better risk assessment and targeted management strategies.

Gut microbiome as a treatment in colorectal cancer.

BACKGROUND: The gut microbiome plays a role in the development and progression of colorectal cancer (CRC). AIM AND OBJECTIVE: This review focuses on whether the gut microbiome is involved in the development and regulation of the host immune system. METHODS: The gut microbiome can influence the production and activity of immune cells and molecules that help to maintain the integrity of the intestinal barrier and prevent inflammation. Gut microbiota modulates the anti-cancer immune response. The gut microbiota can influence the function of immune cells, like T cells, that recognize and eliminate cancer cells. Gut microbiota can affect various aspects of cancer progression and the efficacy of various anti-cancer treatments. RESULTS: Gut microbiota provide promise as a potential biomarker to identify the effect of immunotherapy and as a target for modulation to improve the efficacy of immunotherapy in CRC treatment. CONCLUSION: The potential synergistic effect between the gut microbiome and anti-cancer treatment modalities provides an interest in developing strategies to modulate the gut microbiome to improve the efficacy of anti-cancer treatment.

This review focuses on the gut microbiome in the development and regulation of the host immune system. Gut microbiota provides potential biomarkers to identify the effect of immunotherapy and as a target for modulation of immunotherapy in the treatment of CRC. This provides potential synergistic effects between the gut microbiome and anti-cancer treatment modalities.

Application of coconut shell activated carbon filter in vertical subsurface flow constructed wetland for enhanced multi-metal bioremediation and antioxidant response of Salvinia cucullate.

Coconut shell activated carbon (CNSAC) was applied as a filter layer in hybrid vertical subsurface flow constructed wetland (H-VSSF-CW), in order to enhance the multi-metal removal efficiency of the constructed wetland (CW) and to reduce heavy metal accumulation on Salvinia cucullata. Treatment P + AC, (having CNSAC filter layer), showed 32, 21 and 34% more Cd, Cr, and Pb removal efficiency than treatment P (without CNSAC layer). CNSAC activated carbon adsorbed Cd and Pb and Cr by functional groups -NH, -NO2, -C-O, -OH and -CO, and significantly reduced Cd and Pb exposure to S. cucullate. Chromium adsorption by CNSAC filter layer was half (just 25% of total input) of the Cd and Pb. In treatment P, due to high Cd, Pb and Cr accumulation in S. cucullate, the antioxidant defense mechanism of the plant was collapsed and cell death was observed, which in turn has resulted reduced biomass gain (5% reduction). On the other hand, in treatment P + AC, an antioxidant defense mechanism was active in the form significantly (p ≤ 0.05) increased of SOD, CAT and proline content while reduced MDA, EL, %EB and soluble sugar. So, the application of CNSAC increased the heavy metal removal efficiency of H-VSSF-CW by adsorption of a considerable share of heavy metal and hence, reduced the heavy metal load/exposure to S. cucullate.