CDCA8, a mitosis-related gene, as a prospective pan-cancer biomarker: implications for survival prognosis and oncogenic immunology.

BACKGROUND: Human cell division cycle-associated protein 8 (CDCA8), a critical regulator of mitosis, has been identified as a prospective prognostic biomarker in several cancer types, including breast, colon, and lung cancers. This study analyzed the diagnostic/prognostic potential and clinical implications of CDCA8 across diverse cancers. METHODS: Bioinformatics and molecular experiments. RESULTS: Analyzing TCGA data via TIMER2 and GEPIA2 databases revealed significant up-regulation of CDCA8 in 23 cancer types compared to normal tissues. Prognostically, elevated CDCA8 expression correlated with poorer overall survival in KIRC, LUAD, and SKCM, emphasizing its potential as a prognostic marker. UALCAN analysis demonstrated CDCA8 up-regulation based on clinical variables, such as cancer stage, race, and gender, in these cancers. Epigenetic exploration indicated reduced CDCA8 promoter methylation levels in Kidney Renal Clear Cell Carcinoma (KIRC), Lung Adenocarcinoma (LUAD), and Skin Cutaneous Melanoma (SKCM) tissues compared to normal controls. Promoter methylation and mutational analyses showcased a hypomethylation and low mutation rate for CDCA8 in these cancers. Correlation analysis revealed positive associations between CDCA8 expression and infiltrating immune cells, particularly CD8+ and CD4+ T cells. Protein-protein interaction (PPI) network analysis unveiled key interacting proteins, while gene enrichment analysis highlighted their involvement in crucial cellular processes and pathways. Additionally, exploration of CDCA8-associated drugs through DrugBank presented potential therapeutic options for KIRC, LUAD, and SKCM. In vitro validation using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) confirmed elevated CDCA8 expression in LUAD cell lines (A549 and H1299) compared to control cell lines (Beas-2B and NL-20). CONCLUSION: This study provides concise insights into CDCA8's multifaceted role in KIRC, LUAD, and SKCM, covering expression patterns, diagnostic and prognostic relevance, epigenetic regulation, mutational landscape, immune infiltration, and therapeutic implications.

Cadmium and lead accumulation in important food crops due to wastewater irrigation: Pollution index and health risks assessment.

The contamination of farm soils with heavy metals (HMs) has raised significant concerns due to the increased bioavailability and accumulation of HMs in agricultural food crops. To address this issue, a survey experiment was conducted in the suburbs of Multan and Faisalabad to investigate the spatial distribution, bioaccumulation, translocation, and health risks of cadmium (Cd) and lead (Pb) in agricultural crops. The results show a considerable concentration of Cd and Pb in soils irrigated with wastewater, even though these levels were below the permissible limits in water and soil matrices. The pollution index for Cd was mostly greater than 1 at the selected sites, indicating its accumulation in soil over time due to wastewater irrigation. Conversely, the pollution index for Pb was below 1 at all sites. Among the plants, Zea mays accumulated the highest concentration of Cd and Pb. The translocation factor from soil to root was highest for Brassica olearecea (7.037 for Cd) and Zea mays (6.383 for Pb). The target hazard quotient (THQ) value of Cd exceeded the non-carcinogenic limit for most vegetables. The highest value was found in Allium cepa (5.256) and the lowest in Allium sativum (0.040). In contrast, the THQ level of Pb was below the non-carcinogenic limit for most vegetables, except for Allium cepa (1.479), Solanum lycopersicum (1.367), and Solanum tuberosum (1.326). The study highlights that Allium cepa poses the highest health risk for humans, while Medicago sativa poses the highest risk for animals due to Cd and Pb contamination. These results underscore the urgent need for effective measures to mitigate the health risks associated with HM contamination in crops and soils.

Mechanical Performance of Glass/Epoxy Composites Loaded with Silane-Treated Aluminum Hydroxide Fillers.

This study investigates the influence of silane-treated aluminum hydroxide on the mechanical performance of flame-retardant composites. These composites have potential applications for luggage bags, as a replacement for conventional plastics, offering more durability and lighter weight. Glass fabric was used as the reinforcement, while epoxy was used as the matrix material. To impart flame retardancy, aluminum hydroxide nanoparticles were used as fillers in different weight % age (5%, 10% and 15%). As these are inorganic particles and have compatibility issues with the matrix material, silane-coupling agents (Dynasylan® 6490 and Dynasylan Glymo) were used to treat these filler particles. Both the silane-coupling agents fraction used for treatment and the fillers fraction added to the composites were varied to determine the most optimum combination. The mechanical properties of the developed composites such as tensile, flexural, and short beam shear strength were investigated. The best results were exhibited by 10% aluminum hydroxide fillers treated with 1% (by weight) coupling agent (Dynasylan Glymo).

De novo missense variants in phosphatidylinositol kinase PIP5KIγ underlie a neurodevelopmental syndrome associated with altered phosphoinositide signaling.

Phosphoinositides (PIs) are membrane phospholipids produced through the local activity of PI kinases and phosphatases that selectively add or remove phosphate groups from the inositol head group. PIs control membrane composition and play key roles in many cellular processes including actin dynamics, endosomal trafficking, autophagy, and nuclear functions. Mutations in phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2] phosphatases cause a broad spectrum of neurodevelopmental disorders such as Lowe and Joubert syndromes and congenital muscular dystrophy with cataracts and intellectual disability, which are thus associated with increased levels of PI(4,5)P2. Here, we describe a neurodevelopmental disorder associated with an increase in the production of PI(4,5)P2 and with PI-signaling dysfunction. We identified three de novo heterozygous missense variants in PIP5K1C, which encodes an isoform of the phosphatidylinositol 4-phosphate 5-kinase (PIP5KIγ), in nine unrelated children exhibiting intellectual disability, developmental delay, acquired microcephaly, seizures, visual abnormalities, and dysmorphic features. We provide evidence that the PIP5K1C variants result in an increase of the endosomal PI(4,5)P2 pool, giving rise to ectopic recruitment of filamentous actin at early endosomes (EEs) that in turn causes dysfunction in EE trafficking. In addition, we generated an in vivo zebrafish model that recapitulates the disorder we describe with developmental defects affecting the forebrain, including the eyes, as well as craniofacial abnormalities, further demonstrating the pathogenic effect of the PIP5K1C variants.

The Protective Nature of Gold During Times of Oil Price Volatility: An Analysis of the COVID-19 Pandemic.

This research explores gold's safe-haven properties amid oil price instability, focusing on the COVID-19 pandemic. The study examines how gold hedges against oil price swings in the context of the pandemic's exceptional market circumstances. A VAR (Vector Autoregressive) model analyzes gold and oil prices from 2006 through 2021. The VAR model reflects the dynamic interactions and interdependencies between these two essential commodities in the context of oil price volatility and the COVID-19 pandemic. This analysis shows that gold protects against oil price volatility and the COVID-19 pandemic-gold buffers against oil price swings due to its strong inverse association with oil prices. Gold offers investors security and asset preservation during significant oil price volatility. In light of oil price volatility and the COVID-19 pandemic, the study helps explain gold's importance as a diversification tool and haven asset. Investors, policymakers, and market players should consider gold as a hedge against oil price volatility and economic instability.

Two novel homozygous variants of ATP6V0A2 and ALDH18A1 lead to autosomal recessive cutis laxa type 2 and 3 in two Pakistani families.

BACKGROUND: Autosomal recessive cutis laxa type 2A (ARCL2A; OMIM: 219200) is characterized by neurovegetative, developmental and progeroid elastic skin anomalies. It is caused by biallelic variation in ATPase, H+ transporting V0 subunit A2 (ATP6V0A2; OMIM: 611716) located on chromosome 12q24.31. Autosomal recessive cutis laxa type 3A (ARCL3A; OMIM: 219150) is another subclinical type characterized by short stature, ophthalmological abnormalities and a progeria-like appearance. The ARCL3A is caused by loss of function alterations in the aldehyde dehydrogenase 18 family member A1 (ALDH18A1; OMIM: 138250) gene located at chromosome 10q24.1. METHODS: Whole-exome sequencing (WES), and Sanger sequencing were performed for molecular diagnosis. 3D protein modeling was performed to investigate the deleterious effect of the variant on protein structure. RESULTS: In this study, clinical and molecular diagnosis were performed for two families, ED-01 and DWF-41, which displayed hallmark features of ARCL2A and ARCL3A, respectively. Three affected individuals in the ED-01 family (IV-4, IV-5 and V-3) displayed sagging loose skin, down-slanting palpebral fissures, excessive wrinkles on the abdomen, hands and feet, and prominent veins on the trunk. Meanwhile the affected individuals in the DWF-41 family (V-2 and V-3) had progeroid skin, short stature, dysmorphology, low muscle tone, epilepsy, lordosis, scoliosis, delayed puberty and internal genitalia. WES in the index patient (ED-01: IV-4) identified a novel homozygous deletion (NM_012463.3: c.1977_1980del; p.[Val660LeufsTer23]) in exon 16 of the ATP6V0A2 while in DWF-41 a novel homozygous missense variant (NM_001323413.1:c.1867G>A; p.[Asp623Asn]) in exon 15 of the ALDH18A1 was identified. Sanger validation in all available family members confirmed the autosomal recessive modes of inheritances in each family. Three dimensional in-silico protein modeling suggested deleterious impact of the identified variants. Furthermore, these variants were assigned class 1 or "pathogenic" as per guidelines of American College of Medical Genetics 2015. Screening of ethnically matched healthy controls (n = 200 chromosomes), excluded the presence of these variations in general population. CONCLUSIONS: To the best of our knowledge, this is the first report of ATP6V0A2 and ALDH18A1 variations in the Pakhtun ethnicity of Pakistani population. The study confirms that WES can be used as a first-line diagnostic test in patients with cutis laxa, and provides basis for population screening and premarital testing to reduce the diseases burden in future generations.

AMFR dysfunction causes autosomal recessive spastic paraplegia in human that is amenable to statin treatment in a preclinical model.

Hereditary spastic paraplegias (HSP) are rare, inherited neurodegenerative or neurodevelopmental disorders that mainly present with lower limb spasticity and muscle weakness due to motor neuron dysfunction. Whole genome sequencing identified bi-allelic truncating variants in AMFR, encoding a RING-H2 finger E3 ubiquitin ligase anchored at the membrane of the endoplasmic reticulum (ER), in two previously genetically unexplained HSP-affected siblings. Subsequently, international collaboration recognized additional HSP-affected individuals with similar bi-allelic truncating AMFR variants, resulting in a cohort of 20 individuals from 8 unrelated, consanguineous families. Variants segregated with a phenotype of mainly pure but also complex HSP consisting of global developmental delay, mild intellectual disability, motor dysfunction, and progressive spasticity. Patient-derived fibroblasts, neural stem cells (NSCs), and in vivo zebrafish modeling were used to investigate pathomechanisms, including initial preclinical therapy assessment. The absence of AMFR disturbs lipid homeostasis, causing lipid droplet accumulation in NSCs and patient-derived fibroblasts which is rescued upon AMFR re-expression. Electron microscopy indicates ER morphology alterations in the absence of AMFR. Similar findings are seen in amfra-/- zebrafish larvae, in addition to altered touch-evoked escape response and defects in motor neuron branching, phenocopying the HSP observed in patients. Interestingly, administration of FDA-approved statins improves touch-evoked escape response and motor neuron branching defects in amfra-/- zebrafish larvae, suggesting potential therapeutic implications. Our genetic and functional studies identify bi-allelic truncating variants in AMFR as a cause of a novel autosomal recessive HSP by altering lipid metabolism, which may potentially be therapeutically modulated using precision medicine with statins.

Homozygous Missense Variant in the Solute Carrier Organic Anion Transporter 2A1 (SLCO2A1) Gene Underlies Isolated Nail Clubbing.

BACKGROUND: Inherited isolated nail clubbing is a very rare Mendelian condition in humans, characterized by enlargement of the terminal segments of fingers and toes with thickened nails. Mutations in two genes have been reported to cause isolated nail clubbing in humans, which are the SLCO2A1 gene and the HPGD gene. OBJECTIVES: An extended Pakistani family having two affected siblings born of unaffected consanguineous union was included in the study. Predominant isolated congenital nail clubbing (ICNC) without any other systemic abnormalities was observed, which we aimed to characterize at clinico-genetic level. METHODS: Whole exome coupled with Sanger sequencing were employed to uncover the sequence variant as a cause of the disease. Furthermore, protein modeling was carried out to reveal the predicted possible effect of the mutation at the protein level. RESULTS: Whole exome sequencing data analysis revealed a novel biallelic sequence variant (c.155T>A; p.Phe52Tyr) in the SLCO2A1 gene. Further, Sanger sequencing analysis validated and confirmed the segregation of the novel variant in the entire family. Subsequently, protein modeling of the wild-type and mutated SLCO2A1 revealed broad-scale change, which might compromise the proteins' secondary structure and function. CONCLUSION: The present study adds another mutation to the SLCO2A1-related pathophysiology. The involvement of SLCO2A1 in the pathogenesis of ICNC may open exciting perceptions of this gene in nail development/morphogenesis.

Skin Cancer Classification Using Deep Spiking Neural Network.

Skin cancer is one of the primary causes of death globally, and experts diagnose it by visual inspection, which can be inaccurate. The need for developing a computer-aided method to aid dermatologists in diagnosing skin cancer is highlighted by the fact that early identification can lower the number of deaths caused by skin malignancies. Among computer-aided techniques, deep learning is the most popular for identifying cancer from skin lesion images. Due to their power-efficient behavior, spiking neural networks are attractive deep neural networks for hardware implementation. We employed deep spiking neural networks using the surrogate gradient descent method to classify 3670 melanoma and 3323 non-melanoma images from the ISIC 2019 dataset. We achieved an accuracy of 89.57% and an F1 score of 90.07% using the proposed spiking VGG-13 model, which is higher than the VGG-13 and AlexNet using less trainable parameters.

Effect of farmyard manure, elemental sulphur and EDTA on growth and phytoextraction of cadmium by spider plants (Chlorophytum comosum L.) under Cd stress.

Cadmium (Cd) contamination is considered as a widespread concern at global scale which is serious threats to human health. Phytoremediation is an eco-friendly approach which can remove or immobilize Cd from the soil. Different organic and inorganic amendments can potentially enhance Cd phytoremediation efficiency but the comparison of farmyard manure (FM), elemental sulphur (S) and ethylenediaminetetraacetic acid (EDTA) for Cd phytoremediation through spider plants (Chlorophytum comosum L.) remained unanswered. The present study evaluated the efficiency of S (0.1 and 0.2%), EDTA (0.1 and 0.2%, represented as EDTA-0.1 and EDTA-0.2) and FM (0.5 and 1%, represented as FM-0.5 and FM-1) for remediation of Cd contaminated soils (50 and 100 mg kg-1, represented as Cd-50 and Cd-100) through spider plants. Results depicted that the highest shoots and roots dry biomass was found in FM treated plants followed by S, EDTA and control except in EDTA-0.2 treatment in which the lowest values of these parameters were observed. Application of FM-1 significantly increased the shoot dry weight (120%), root dry weight (99%), as well as photosynthetic attributes in Cd-50 as compared to control. Application of EDTA-0.2 increased the bioavailable fraction of Cd than control and the maximum increase was observed in Cd-100. The highest Cd concentrations in shoot and roots were found in EDTA treated plants followed by S, control and FM irrespective of Cd and amendment levels. Maximum Cd in roots (109%) and shoots (156%) was recorded in plants grown in Cd-100 with EDTA-0.2 than control. The maximum bioaccumulation factor, translocation index, harvest index and root to shoot translocation were observed with EDTA than control and other treatments. EDTA along with spider plants may enhance the uptake of Cd but lower biomass production in the highest dose of EDTA may questioned the efficiency of EDTA.

Applications of Cinematic Rendering in the Diagnoses of Compressive Complications of Saphenous Venous Graft Pseudoaneurysms: A Pictorial Essay.

Pseudoaneurysms arising from the saphenous venous graft (SVGs) are an uncommon complication of the coronary artery bypass graft (CABG). Although angiography is the gold standard, computed tomography angiography (CTA) of the coronary arteries is the most efficient modality to diagnose these cases and their associated complications. Among numerous possible complications of SVG pseudoaneurysms, local mass effect on the cardiac chambers, adjacent pulmonary vasculature or coronary arteries/bypass grafts have been described. Cinematic rendering, an advanced post-processing technique can be valuable for problem solving in complex cases. In this pictorial essay, we report 3 CT cases of SVG pseudoaneurysms that demonstrate a range of CT imaging appearances of SVG pseudoaneurysms and related complications. Additionally, we will emphasize the applications of cinematic rendering in visualization of complex post-surgical cardiovascular pathology. This manuscript is designed as a pictorial essay of 3 complex cases given the relative uncommon nature of this pathology and the availability of cinematic rendering as an advanced post-processing modality. We demonstrated 3 imaging examples of utilization of cinematic rendering (CR) to demonstrate complex anatomical details of the mass-effect and compression related complications associated with SVG pseudoaneurysms. A side-by-side comparison with conventional volume rendering (VR) is also performed in 1 case for perspective and to show improved comparative visual appeal of the CR given better depth perception and more natural appearing illumination. The technical differences of the 2 techniques are also briefly discussed.

Prostatic adenocarcinoma in a patient with persistent Müllerian duct syndrome.

The embryonal male sexual differentiation is driven by testosterone, and Anti-Müllerian hormone (AMH). AMH is responsible for regression of Müllerian ducts in a genetically male fetus. Mutations inactivating AMH or its receptors are responsible for persistent Müllerian duct syndrome (PMDS) in virilized 46, XY males. PMDS is a rare genetic disorder affecting males, with less than 300 cases described in literature. The syndrome is usually recognized early in life with patients present with bilateral undescended testicles, and often decreased testosterone production by Leydig cells later in life. The role of testosterone in the development and progression of prostate cancer is well established, and men with low circulating free testosterone are expected to have a lower risk of developing prostate cancer. Indeed, 2 cases of prostate cancer in patients with PMDS have previously been described. Herein, we are reporting the third of prostate cancer in patient with PMDS.

Short-Term Efficacy Of Intravitreal Patizra® (Ranibizumab) In Treatment Naive Patients- Real World Evidence In Pakistan.

Background: : Macular oedema is a final common pathway of a multitude of both ocular and systemic insults. This study was conducted to evaluate the short-term efficacy and safety of intraocular Ranibizumab in patients with macular oedema in a 'real-world' setting in Pakistan. Methods: A prospective multicenter study conducted at Amanat Eye Hospitals in Islamabad and Rawalpindi from 1st August 2018 to 1st November 2019. Forty-four eyes of 34 patients with macular oedema were treated with monthly intravitreal Ranibizumab (Patizra® ) injections for three consecutive months. Best-corrected visual acuity (BCVA), and optical coherence tomography (OCT) parameters including central retinal thickness (CRT) and macular volume were assessed prior to the injections and then 4 weeks post the final injection and compared. Results: BCVA improved from logMAR 0.61±0.40 at baseline to 0.27±0.35 four weeks after the third intravitreal injection. CRT decreased from 428.54±187.06 µm at baseline to 364.50±170.49 µm. Macular volume showed a non-significant decrease from 9.97±3.19 mm3 at baseline to 9.22±2.68 mm3 four weeks after the third intravitreal injection. No systemic or ocular complications were observed during the course of the study. Conclusion: Treatment with intravitreal Patizra® injections was found safe and resulted in clinically and statistically significant improvement in visual acuity and the SD-OCT parameter of central retinal thickness in patients with macular oedema secondary to various retinal pathologies. There was no significant decrease in the macular volume.

Metabolic Profiling by GC-MS, In Vitro Biological Potential, and In Silico Molecular Docking Studies of Verbena officinalis.

Verbena officinalis L. is a traditionally important medicinal herb that has a rich source of bioactive phytoconstituents with biological benefits. The objective of this study was to assess the metabolic profile and in vitro biological potential of V. officinalis. The bioactive phytoconstituents were evaluated by preliminary phytochemical studies, estimation of polyphenolic contents, and gas chromatography-mass spectrometry (GC-MS) analysis of all fractions (crude methanolic, n-hexane, ethyl acetate, and n-butanol) of V. officinalis. The biological investigation was performed by different assays including antioxidant assays (DPPH, ABTS, CUPRAC, and FRAP), enzyme inhibition assays (urease and α-glucosidase), and hemolytic activity. The ethyl acetate extract had the maximum concentration of total phenolic and total flavonoid contents (394.30 ± 1.09 mg GAE·g-1 DE and 137.35 ± 0.94 mg QE·g-1 DE, respectively). Significant antioxidant potential was observed in all fractions by all four antioxidant methods. Maximum urease inhibitory activity in terms of IC50 value was shown by ethyl acetate fraction (10 ± 1.60 µg mL-1) in comparison to standard hydroxy urea (9.8 ± 1.20 µg·mL-1). The n-hexane extract showed good α-glucosidase inhibitory efficacy (420 ± 20 µg·mL-1) as compared to other extract/fractions. Minimum hemolytic activity was found in crude methanolic fraction (6.5 ± 0.94%) in comparison to positive standard Triton X-100 (93.5 ± 0.48%). The GC-MS analysis of all extract/fractions of V. officinalis including crude methanolic, n-hexane, ethyl acetate, and n-butanol fractions, resulted in the identification of 24, 56, 25, and 9 bioactive compounds, respectively, with 80% quality index. Furthermore, the bioactive compounds identified by GC-MS were analyzed using in silico molecular docking studies to determine the binding affinity between ligands and enzymes (urease and α-glucosidase). In conclusion, V. officinalis possesses multiple therapeutical potentials, and further research is needed to explore its use in the treatment of chronic diseases.

Royal Jelly: Beneficial Properties and Synergistic Effects with Chemotherapeutic Drugs with Particular Emphasis in Anticancer Strategies.

Cancer is one of the major causes of death globally. Currently, various methods are used to treat cancer, including radiotherapy, surgery, and chemotherapy, all of which have serious adverse effects. A healthy lifestyle, especially a nutritional diet, plays a critical role in the treatment and prevention of many disorders, including cancer. The above notion, plus the trend in going back to nature, encourages consumers and the food industry to invest more in food products and to find potential candidates that can maintain human health. One of these agents, and a very notable food agent, is royal jelly (RJ), known to be produced by the hypopharyngeal and mandibular salivary glands of young nurse honeybees. RJ contains bioactive substances, such as carbohydrates, protein, lipids, peptides, mineral salts and polyphenols which contribute to the appreciated biological and pharmacological activities. Antioxidant, anticancer, anti-inflammatory, antidiabetic, and antibacterial impacts are among the well-recognized benefits. The combination of RJ or its constituents with anticancer drugs has synergistic effects on cancer disorders, enhancing the drug's effectiveness or reducing its side effects. The purpose of the present review is to emphasize the possible interactions between chemotherapy and RJ, or its components, in treating cancer illnesses.

A Primer to Cost-Effectiveness Analysis in Breast Cancer Imaging: A Review of the Literature.

Currently, there is a multitude of methods for evaluating the costs and benefits of programs, tools, etc. While cost-benefit analysis (CBA) is commonly used, cost-effectiveness analysis (CEA) is a more appropriate method of evaluation in clinical contexts, such as radiology practices, as CEAs use units such as life years gained as opposed to money (as is the case for CBAs). This review examines CEAs performed within the past 15 years to highlight their applications and key findings in the context of medical imaging. In total, 20 articles published between 2006 and 2022 were identified using a PubMed search for keywords including "cost-effectiveness analysis," "breast cancer," and "medical imaging," with studies lacking a substantial discussion of CEA or a related topic being excluded. CEAs have traditionally been criticized for lack of a standard methodology, despite their utility in the detection and treatment of various pathologies. Although mammography and magnetic resonance imaging (MRI) are the preferred and cost-effective imaging modalities for breast cancer, other imaging modalities, such as contrast-enhanced mammography and digital breast tomosynthesis, may be more cost-effective in the appropriate clinical context. Different combinations of mammography and MRI screenings for certain breast cancers may also prove to be more cost-effective compared to current mammography/MRI screening schedules. While CEA has shown potential utility in estimating the costs (per unit of health gained) of different imaging tools, CEA risks ignoring important outcomes not included in the analysis and cannot address if the benefits of the imaging tool exceed its costs, as a CBA would, suggesting the need for combining several economic evaluations for a more complete understanding.

Expression variation of OGG1 and HPRT gene and DNA damage in arsenic exposed industrial workers.

Arsenic exposure alters redox balance, induces DNA damage, and deregulates many genes. OGG1 gene involved in base repair mechanism, for excision of 8-oxoguanine (8-oxoG) from DNA formed as a result of accumulation of ROS in cell. HPRT gene encode transferase enzymes involved in purine recycling mechanism. The main focus of the study was to evaluate the expression variation in HPRT, OGG1 gene expression, and DNA damage of industrial workers. Blood samples of 300 occupational workers were collected from welding, brick kiln, furniture, pesticide, and paint industry (n = 60/industry) to evaluate the expression variation in HPRT, OGG1 gene expression, and DNA damage in blood cells by comet assay along with age and gender matched 300 control individuals. Blood arsenic content was higher (P<0.001) in an industrial group compared to the control. OGG1 and HPRT expression were (P<0.05) downregulated in exposed workers compared to controls. Spearman correlation analysis showed a significant positive correlation between HPRT vs OGG1 (P< 0.0001) in exposed workers compared to controls. Altered expression of both genes was observed between workers with <25years and >25years of age as well as between workers with <10years and >10year exposure. Reduced expression (P<0.05) of both genes and a high extent of DNA damage was evident in exposed smokers compared to respective non-smokers. DNA fragmentation was higher (P<0.05) in the furniture, welding and brick kiln group compared to control, and other industries. The present study suggests that altered expression of OGG1 and HPRT gene induce oxidative stress, showed a negative impact on the recycling of purines leading to DNA damage which increase the vulnerability of workers to carcinogenicity.

Chemical Profiling, Formulation Development, In Vitro Evaluation and Molecular Docking of Piper nigrum Seeds Extract Loaded Emulgel for Anti-Aging.

Emulgel is a new innovatory technique for drug development permitting controlled release of active ingredients for topical administration. We report a stable emulgel of 4% Piper nigrum extract (PNE) prepared using 80% ethanol. The PNE-loaded formulation had an antioxidant activity of 84% and tyrosinase inhibition was 82%. Prepared formulation rendered spherical-shaped globules with high zeta potential (-45.5 mV) indicative of a stable system. Total phenolic contents were 58.01 mg GAE/g of dry extract whereas total flavonoid content was 52.63 mg QE/g of dry extract. Sun protection factor for PNE-loaded emulgel was 7.512 and formulation was stable without any evidence of physical and chemical changes following 90 days of storage. Gas chromatography-mass spectroscopy (GC-MS) revealed seventeen bioactive compounds in the PNE including monoterpenoids, triterpenoids, a tertiary alcohol, fatty acid esters, and phytosterols. In silico studies of GC-MS identified compounds show higher binding affinity in comparison to standard kojic acid indicating tyrosinase inhibition. It can be concluded that PNE-loaded emulgel had prominent antioxidant and tyrosinase inhibition and can be utilized as a promising topical system for anti-aging skin formulation.

Cultural and Medicinal Use of Amphibians and Reptiles by Indigenous People in Punjab, Pakistan with Comments on Conservation Implications for Herpetofauna.

Amphibians and reptiles have interacted with humans for millennia. However, humans interact with amphibian and reptile species in different manners, which depend on their culture and traditions. This study was designed to better understand the interactions between amphibian and reptile species and their usage among the native peoples in the vicinity of the Jhelum and Chenab rivers, Pakistan. Information was collected through semi-structured interviews and questionnaires, and was analyzed by using different indices, including the frequency of citation, corrected fidelity level, fidelity level, relative importance level, and informant major ailment. Two amphibians and twenty-six reptile species were used in therapeutic medicine in the study area. Based on the cultural analysis, we found that Naja naja (black cobra) was highly cited across all cultural groups. A 100% Fidelity Level was calculated for the following species: Naja naja (eye infection), Varanus bengalensis (joint pain), Eurylepis taeniolatus (cataract), and Acanthodactylus cantoris (cancer). We found five endangered species in the study area, i.e., Aspideretes gangeticus, A. hurum, Chitra indica, Varanus flavescens, and Geoclemys hamiltonii, that were used to cure joint pain, muscle stretching and pain, backbone pain, paralysis, and psoriasis, respectively. Likewise, Lissemys punctata andersoni, a vulnerable species as labelled by the International Union for Conservation of Nature, was extensively used for the treatment of joint pain, body pain, paralysis, and arthritis in the study area. In terms of conservation, it is critical to protect the highly vulnerable and endangered species that are being used in therapeutic medicines. Our findings may be helpful for the conservation of amphibian and reptile species by helping to make an effective plan to prevent their extinction. The main threats to the diversity of amphibian and reptile species in the area are hunting, trading, and cultural use. These threats could potentially lead to the extinction of these species. Therefore, with the involvement of concerned authorities, e.g., local stakeholders, the Ministry of Climate Change, provincial wildlife departments, academia, and conservation managers, immediate conservation measures should be taken for the protection and sustainable utilization of medicinal species.

Medicinal waterbirds in the traditional healthcare system: an assessment of biodiversity-cultural linkages in Eastern Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Eastern Khyber Pakhtunkhwa is home to a vast range of medicinal and edible waterbird species due to its diverse geographical environment. Waterbird species have been used for various ailments and cultural practices since ancient times, while ethno-pharmacological applications and cultural uses of waterbird species in this area have seldom been documented. This study is the first ethnomedicinal and cultural assessment of waterbird species, and the first compilation and listing of all known data on these species in Eastern Khyber Pakhtunkhwa, Pakistan. METHODS: Interviews and questionnaires were used to collect data from native respondents (N = 100). To analyze the data, principal component analysis (PCA), relative frequency of citation (RFC), fidelity level (FL%), relative popularity level (RPL), rank order priority, and similarity index were used. RESULTS: In total, 64 waterbird species were utilized in cultural practices, of which 40 species are used to cure different infectious and chronic diseases such as cold, cough, flu, fever, respiratory disorders, asthma, TB, gastric ulcers, kidney stones, male impotency, obesity, paralysis, piles, cancer, arthritis, body pain, and weakness. PCA showed significant differences in the use of waterbird species among the local inhabitants of the study area, separated along the axis-2 (p < 0.05). The FL% of waterbird species varied from 12 to 100%. 100% FL was analyzed for four waterbird species, i.e., Charadrius mongolus (cold), Gallicrex cinerea (asthma), Anas platyrhynchos (cancer), and Esacus recurvirostris (body weakness). In this study, Mallard (Anas platyrhynchos) was the most popular species used in the healthcare system of Eastern Khyber Pakhtunkhwa, with high RFC (4.06), FL% (100), and RPL (1.0) values. CONCLUSION: We concluded that waterbird species are more used for medicine and food purposes in the study area. However, in vitro/in vivo assessment of biochemical activities of waterbird species with a maximum FL% might be significant to produce novel drugs. Recent research shows important ethno-ornithological information about native people and their links with waterbird species, which might be helpful for the sustainable use of waterbird diversity in the research area.