Insights into Nimbolide molecular crosstalk and its anticancer properties.

Nimbolide, one of the main ingredients constituent of Azadirachta indica (neem) leaf extract, has garnered attention for its potential as an anticancer agent. Its efficacy against various cancers and chemopreventive action has been demonstrated through numerous in vivo and in vitro studies. This updated review aims to comprehensively explore the chemopreventive and anticancer properties of nimbolide, emphasizing its molecular mechanisms of action and potential therapeutic applications in oncology. The review synthesizes evidence from various studies that examine nimbolide's roles in apoptosis induction, anti-proliferation, cell death, metastasis inhibition, angiogenesis suppression, and modulation of carcinogen-metabolizing enzymes. Nimbolide exhibits multifaceted anticancer activities, including the modulation of multiple cell signaling pathways related to inflammation, invasion, survival, growth, metastasis, and angiogenesis. However, its pharmacological development is still in the early stages, mainly due to limited pharmacokinetic and comprehensive long-term toxicological studies. Nimbolide shows promising anticancer and chemopreventive properties, but there is need for systematic preclinical pharmacokinetic and toxicological research. Such studies are essential for establishing safe dosage ranges for first-in-human clinical trials and further advancing nimbolide's development as a therapeutic agent against various cancers. The review highlights the potential of nimbolide in cancer treatment and underscores the importance of rigorous preclinical evaluation to realize its full therapeutic potential.

Synthesis of the chromone-thiosemicarbazone scaffold as promising α-glucosidase inhibitors: An in vitro and in silico approach toward antidiabetic drug design.

Diabetes is a serious metabolic disorder affecting individuals of all age groups and prevails globally due to the failure of previous treatments. This study aims to address the most prevalent form of type 2 diabetes mellitus (T2DM) by reporting on the design, synthesis, and in vitro as well as in silico evaluation of chromone-based thiosemicarbazones as potential α-glucosidase inhibitors. In vitro experiments showed that the tested compounds were significantly more potent than the standard acarbose, with the lead compound 3n exhibiting an IC50 value of 0.40 ± 0.02 µM, ~2183-fold higher than acarbose having an IC50 of 873.34 ± 1.67 µM. A kinetic mechanism analysis demonstrated that compound 3n exhibited reversible inhibition of α-glucosidase. To gain deeper insights, in silico molecular docking, pharmacokinetics, and molecular dynamics simulations were conducted for the investigation of the interactions, orientation, stability, and conformation of the synthesized compounds within the active pocket of α-glucosidase.

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.

A Novel EPC1::KDM2B Fusion in High-grade Endometrial Stromal Sarcoma.

The spectrum of endometrial stromal sarcoma (ESS) has expanded substantially since the publication of the most recent World Health Organisation (WHO) Classification of Female Genital Tumours and the advent of widely available genomic testing. We describe a uterine mesenchymal tumor harboring a novel EPC1::KDM2B fusion, best classified within the umbrella of high-grade endometrial stromal sarcoma (HGESS). This tumor was composed of a uniform population of spindled cells with some myxoid stroma, a mitotic rate of up to 21/10 high-power fields, and a largely pushing margin with focal vascular invasion. Immunohistochemistry showed strong and diffuse cyclin D1 positivity while CD10, WT1, DOG1, CD117, CD34, CD99, S100, MelanA, SMA, desmin, and h-caldesmon were negative. The tumor was confined to the uterus and no recurrence has been detected thus far, albeit with a short follow-up interval of 9 mo.

Perfect single-photon sources.

We introduce the gapped coherent state in the form of a single-photon source (SPS) that consists of uncorrelated photons as a background, except that we demand that no two photons can be closer in time than a time gap [Formula: see text]. While no obvious quantum mechanism is yet identified to produce exactly such a photon stream, a numerical simulation is easily achieved by first generating an uncorrelated (Poissonian) signal and then for each photon in the list, either adding such a time gap or removing all photons that are closer in time from each other than [Formula: see text]. We study the statistical properties of such a hypothetical signal, which exhibits counter-intuitive features. This provides a neat and natural connection between continuous-wave (stationary) and pulsed single-photon sources, with also a bearing on what it means for such sources to be perfect in terms of single-photon emission.

Designing, cloning and simulation studies of cancer/testis antigens based multi-epitope vaccine candidates against cutaneous melanoma: An immunoinformatics approach.

Background: Melanoma is the most fatal kind of skin cancer. Among its various types, cutaneous melanoma is the most prevalent one. Melanoma cells are thought to be highly immunogenic due to the presence of distinct tumor-associated antigens (TAAs), which includes carcinoembryonic antigen (CEA), cancer/testis antigens (CTAs) and neo-antigens. The CTA family is a group of antigens that are only expressed in malignancies and testicular germ cells. Methods: We used integrative framework and systems-level analysis to predict potential vaccine candidates for cutaneous melanoma involving epitopes prediction, molecular modeling and molecular docking to cross-validate the binding affinity and interaction between potential vaccine agents and major histocompatibility molecules (MHCs) followed by molecular dynamics simulation, immune simulation and in silico cloning. Results: In this study, three cancer/testis antigens were targeted for immunotherapy of cutaneous melanoma. Among many CTAs that were studied for their expression in primary and malignant melanoma, NY-ESO-1, MAGE1 and SSX2 antigens are most prevalent in cutaneous melanoma. Cytotoxic and Helper epitopes were predicted, and the finest epitopes were shortlisted based on binding score. The vaccine construct was composed of the four epitope-rich domains of antigenic proteins, an appropriate adjuvant, His tag and linkers. This potential multi-epitope vaccine was further evaluated in terms of antigenicity, allergencity, toxicity and other physicochemical properties. Molecular interaction estimated through protein-protein docking unveiled good interactions characterized by favorable binding energies. Molecular dynamics simulation ensured the stability of docked complex and the predicted immune response through immune simulation revealed elevated levels of antibodies titer, cytokines, interleukins and immune cells (NK, DC and MA) population. Conclusion: The findings indicate that the potential vaccine candidates could be effective immunotherapeutic agents that modify the treatment strategies of cutaneous melanoma.

Role of organic and inorganic amendments on physiological attributes of germinating pea seedlings under arsenic stress.

There are scarce data regarding the effects of soil amendments on biophysicochemical responses of plants at the early stages of growth/germination. This study critically compares the effects of ethylene-diamine-tetra-acetic-acid (EDTA) and calcium (Ca) on biophysicochemical responses of germinating pea seedlings under varied arsenic levels (As, 25, 125, 250 µM). Arsenic alone enhanced hydrogen peroxide (H2O2) level in pea roots (176%) and shoot (89%), which significantly reduced seed germination percentage, pigment contents, and growth parameters. Presence of EDTA and Ca in growth culture minimized the toxic effects of As on pea seedlings, EDTA being more pertinent than Ca. Both the amendments decreased H2O2 levels in pea tissues (16% in shoot and 13% in roots by EDTA, and 7% by Ca in shoot), and maintained seed germination, pigment contents, and growth parameters of peas close to those of the control treatment. The effects of all As-treatments were more pronounced in the pea roots than in the shoot. The presence of organic and inorganic amendments can play a useful role in alleviating As toxicity at the early stages of pea growth. The scarcity of data demands comparing plant biophysicochemical responses at different stages of plant growth (germinating vs mature) in future studies.

Till date, abundant research has focused on plant biophysicochemical responses to different types of pollutants. However, the majority of these studies dealt with pollutant exposure to mature plants (generally after a vegetative growth period of 1­2 weeks). Despite significant research, there are still limited data regarding the biophysicochemical responses of plants at their early stages of germination and growth. In fact, stresses at germination or at an early stage of growth can be highly fatal and may significantly affect the ultimate plant growth and potential to remediate the contaminated sites. Therefore, the current study deals with the exposure of germinating pea seedlings to arsenic (As) stress under varied amendments. This experimental plan helped to understand the initial biophysicochemical changes induced in pea plants under As stress.

Effects of Constraint-Induced Movement Therapy and Application Time and Duration of Intervention for Lower Extremity in Stroke: A Systematic Review.

The primary aim of this review was to determine the effects of CIMT (constraint-induced movement therapy) on gait, balance, and motor functions of the lower extremity in stroke. The secondary aim was to determine the optimal dosage, application time, and duration of CIMT in the lower extremity in stroke. PubMed (1999-July 2021), Pedro (2000-December 2020), Google Scholar (1999-Febraury 2022), and Cochrane Library (2000-Febraury 2022) were searched in February 2022. The risk of bias was calculated through the criteria outlined in the (Cochrane-Handbook for Systematic-Reviews of Interventions). Eight RCTs were included in this review. CIMT was found to be effective in improving balance, gait, and motor functions of lower limbs; however, its superiority in comparison to the control group was not significant, no specific dosage was mentioned for lower limb CIMT as different studies used different durations and intensities of CIMT. Key Words: Cerebrovascular accident (CVA), Balance, Lower-extremity constraint-induced movement therapy (CIMT), Motor functions.

Comparative taxonomical, biological and pharmacological potential of healthy and geminivirus infected leaves of Hibiscus rosa-sinensis L.: First report.

In the present research project, the first report on comparative analysis of the taxonomical, biological and pharmacological potential of healthy and geminivirus infected Hibiscus rosa sinensis (L.) leaves of the family Malvaceae was done by using different micro and macroscopic techniques. First of all, leaves were characterized for Cotton leaf curl Multan virus (CLCuMuV) and its associated betasatellite (Cotton leaf curl Multan Betasatellite; CLCuMB). Different morphological parameters like shape and size of stem, leaves, seeds and roots, presence and absence of ligule, distance between nodes and internodes and type of inflorescence etc. were analyzed. CLCuMuV infected H. rosa-sinensis revealed systematic symptoms of infection like chlorosis of leaves, stunted growth, decrease in size of roots, shoots and distortion etc. Anatomical investigation was performed under light ad scanning electron microscope. Different anatomical features like length and shape of guard cells, subsidiary cells, presence or absence of stomata, secretory ducts and trichomes were examined. In both plant samples anomocytic types of stomata and elongated, non-glandular and pointed tip trichomes were present, but the size (especially length and width) of trichomes and other cells like epidermal, subsidiary, and guard cells were highest in virus infected plants likened to healthy one. In the antibacterial activity, the maximum antibacterial potentail was seen in methanolic extract of K. pneumonea while antifungal activity was shown by methanolic extract of A. solani. Plants interact with different biological entities according to environmental conditions continuously and evolved. These types of interactions induce changes positively and negatively on plant metabolism and metabolites production. Many plant viruses also attacked various host plants consequently alter their secondary metabolism. To overcome such virus infected plants produces many important and different types of secondary plant metabolites as a defense response. Subsequent analysis of this n-hexane plant extract using Gas chromatography mass spectroscopy technique revealed that Hibiscus eluted contained 10 main compounds in Healthy sample and 13 compounds in infected one. Presence of essential secondary metabolites were also analyzed by FTIR analysis. The present study provides a comprehensive and novel review on taxonomy (morphology, anatomy) and antimicrobial potential of both healthy and geminivirus infected H. rosa-sinensis.

Deciphering Molecular Mechanisms of Carbon TetrachlorideInduced Hepatotoxicity (Fibrosis): A Brief Systematic Review.

The liver plays a critical role in metabolic processes, making it vulnerable to injury. Researchers often study carbon tetrachloride (CCl4)-induced hepatotoxicity in model organisms because it closely resembles human liver damage. This toxicity occurs due to the activation of various cytochromes, including CYP2E1, CYP2B1, CYP2B2, and possibly CYP3A, which produce the trichloromethyl radical (CCl3*). CCl3* can attach to biological molecules such as lipids, proteins, and nucleic acids, impairing lipid metabolism and leading to fatty degeneration. It can also combine with DNA to initiate hepatic carcinogenesis. When exposed to oxygen, CCl3* generates more reactive CCl3OO*, which leads to lipid peroxidation and membrane damage. At the molecular level, CCl4 induces the release of several inflammatory cytokines, including TNF-α and NO, which can either help or harm hepatotoxicity through cellular apoptosis. TGF-ß contributes to fibrogenesis, while IL-6 and IL-10 aid in recovery by minimizing anti-apoptotic activity and directing cells toward regeneration. To prevent liver damage, different interventions can be employed, such as antioxidants, mitogenic agents, and the maintenance of calcium sequestration. Drugs that prevent CCl4- induced cytotoxicity and proliferation or enhance CYP450 activity may offer a protective response against hepatic carcinoma.

Biochar supported metallo-inorganic nanocomposite: A green approach for decontamination of heavy metals from water.

Heavy metal contamination of water has become a global environmental burden, which has stirred up agitation worldwide. Fabrication of adsorbents utilizing either low cost, environment friendly materials or waste products can be helpful in remediating environmental pollution. The current study evolved around the synthesis of nanocomposites derived from such raw precursors like spent tea waste biochar, hydroxyapatite, and clays. In this context, two nanocomposites, namely manganese ferrite doped hydroxyapatite/kaolinite/biochar (TK-NC) and manganese ferrite doped hydroxyapatite/vermiculite/biochar (TV-NC), were synthesized followed by their employment for decontamination of heavy metals from aqueous media. TK-NC and TV-NC exhibited the crystallite sizes in the range of 2.55-5.94 nm as obtained by Debye Scherrer Equation and Williamsons-Hall equation The fabricated nanocomposites were characterized using FT-IR, SEM-EDX, and powder XRD. Batch adsorption studies were performed, and influence of different adsorption parameters (contact time, reaction temperature, solution pH, adsorbent dose, and initial adsorbate concentration) on metal adsorption was examined. Thermodynamic studies revealed that the adsorption of Cr(VI), Ni(II) and Cu(II) on TK-NC and TV-NC was endothermic (+ΔH°) and indicates disorderness (+ΔS°) at the solid-liquid interface owing to the strong affinity of metal ions with adsorbent. The heavy metal uptake selectivity followed the following decreasing order; Cr(VI) > Cu(II) > Ni(II) by both nanocomposites, with adsorption capacities falling in the range of 204.68-343.05 mg g-1. Several adsorption kinetic and isotherm models were applied to experimentally calculated data, which suggest favorable adsorption of Cr(VI), Ni(II) and Cu(II) by TK-NC and TV-NC from the system while obeying general-order kinetics and R-P adsorption model, conferring the transition in adsorption kinetics order and involvement of multiple adsorption process.

Arsenic level in groundwater and biological samples in Khanewal, Pakistan.

Groundwater is the most valuable natural source in our earth's planet, being contaminated in various regions worldwide. Despite considerable research, there are scarce data regarding arsenic (As) levels in groundwater and its build-up in biological samples in Pakistan. The current investigation analyzed As contamination in four tehsils of District Khanewal (Kabirwala tehsil, Jahaniyan tehsil, Mian Channu tehsil, and Khanewal tehsil). For that, 123 groundwater samples, 19 animal milk samples, 20 human nails, and 20 human hair samples were collected from the study area. Arsenic concentration in groundwater was up to 51.8 µg/L with an average value of 7.2 µg/L. About 28 water samples (23%) had As contents > WHO limit and 38 samples (31%) > DEP-NJ limit. Low levels of As were detected in biological samples. Average As levels were 23 µg/L in the milk samples and 298 µg/kg in human hair. Arsenic contents were not detected in nail samples, except in one sample from Kabirwala tehsil. The maximum values of hazard quotient and cancer risk in District Khanewal were 4.9 and 0.0022, respectively. It is anticipated that long-term use of As-containing water may led to poisoning of humans in the study area, especially in Kabirwala. Therefore, it is necessary to monitor As contamination in the groundwater of Kabirwala tehsil to reduce the potential health hazards.

Overview of gait rehabilitation in stroke.

Stroke is the 2nd leading cause of death globally after ischaemic heart disease and is expected to rise more by 2030. The estimated incidence of stroke in Pakistan is about 250/100,000 individuals. Difficulty in walking is present in approximately 80% of stroke survivors. About a quarter of stroke survivors, even after receiving rehabilitation have residual gait impairments requiring assistance in activities of daily life. Almost half of stroke patients after being discharged will have episodes of fall, with majority of these falls occurring in activities like "turning". Gait is one of the key features to participate in community and occupational activities. Therefore, appropriate gait rehabilitation post stroke is crucial for functional independence and community ambulation. There are many approaches to gait rehabilitation based on different models of motor physiology and disease. Augmenting conventional therapies with novel techniques such as utilization of electromechanical means have improved gait rehabilitation in improving functions. The usage of technology in rehabilitation of patients with neurological deficits, is still novel in Pakistan. This review provides an overview of advancements in neurological and gait rehabilitation post stroke.

Isolation and characterization of indigenous bacterial assemblage for biodegradation of persistent herbicides in the soil.

Extensive pesticides (herbicides) use is negatively disturbing the environment and humans. Pesticide bioremediation with eco-friendly techniques bears prime importance. This study aimed to isolate and characterize three different herbicides (metribuzin, clodinafop- propargyl, MCPA (2-methyl, 4 chlorophenoxyacetic acids) and Bromoxynil) degrading bacterial strains from agricultural fields of Punjab University, Pakistan. Among the 12 bacterial isolates, 5 were metribuzin degrading, 3 were clodinafop propargyl degrading and, 4 were MCPA and Bromoxynil degrading bacteria. Morphological, microscopic, and molecular characterization revealed that the majority of these bacterial strains were gram-negative and belonged to Bacillus and Pseudomonas genera. The isolates A6, B3, and C1 were subjected to respective herbicide degradation and the data was confirmed through GC-MS analysis. The effect of herbicide concentrations, pH, and temperature on bacterial growth was determined at OD600. The strain A6 degraded 14.8% metribuzin out of the provided concentration of 50 ppm by following the deamination pathway. While the isolates B3 and C1 degraded 23.2% and 33.9% clodinafop, MCPA and bromo-xynil, respectively, at a spiking concentration of 50ppm. The clodinafop, MCPA and Bromoxynil were metabolized into less toxic products i.e., dicarboxylic acids and 2-methyl phenol respectively, and metabolized via decarboxylation and dehalogenation mechanism. The present study evaluates the herbicides degrading bacterial strains that could potentially be used for bioremediation of agricultural contaminated sites.

Effect of freshwater and wastewater irrigation on buildup of toxic elements in soil and maize crop.

Untreated wastewater is routinely used for agricultural activities in water-stressed regions, thereby causing severe ecological risks by various pollutants. Hence, management strategies are needed to cope with the environmental issues related to wastewater use in agriculture. This pot study evaluates the effect of mixing either freshwater (FW) or groundwater (GW) with sewage water (SW) on the buildup of potentially toxic elements (PTEs) in soil and maize crop. Results revealed that SW of Vehari contains high levels of Cd (0.08 mg L-1) and Cr (2.3 mg L-1). Mixing of FW and GW with SW increased soil contents of As (22%) and decreased Cd (1%), Cu (1%), Fe (3%), Mn (9%), Ni (9%), Pb (10%), and Zn (4%) than SW "alone" treatment. Risk indices showed high-degree of soil-contamination and very-high ecological risks. Maize accumulated considerable concentrations of PTEs in roots and shoot with bioconcentration factor > 1 for Cd, Cu, and Pb and transfer factor > 1 for As, Fe, Mn, and Ni. Overall, mixed treatments increased plant contents of As (118%), Cu (7%), Mn (8%), Ni (55%), and Zn (1%), while decreased those of Cd (7%), Fe (5%), and Pb (1%) compared to SW "alone" treatments. Risk indices predicted possible carcinogenic risks to cow (CR 0.003 > 0.0001) and sheep (CR 0.0121 > 0.0001) due to consumption of maize fodder containing PTEs. Hence, to minimize possible environmental/health hazards, mixing of FW and GW with SW can be an effective strategy. However, the recommendation greatly depends on the composition of mixing waters.

Use of agricultural bio-wastes to remove arsenic from contaminated water.

Arsenic (As) is a highly toxic metalloid. High As levels have been recorded in groundwater aquifers at a global scale. This study investigated As level in groundwater of District Vehari and assessed the potential of different agricultural by-products (sugarcane bagasse, cottonseed hulls, soybean hulls, corncobs and rice husk) to remove As from water. The study was carried out in two steps. In the first step, a total of 38 groundwater samples were obtained from Vehari. Groundwater samples were analyzed for total As contents and physicochemical parameters. Results indicated that As content ranged from below detection limit to 49 µg/L in the groundwater samples. The values of hazard quotient and cancer risk were up to 1.5 and 0.0004, respectively, which delineated severe risk of As poisoning. During the second step, six As-contaminated groundwater samples (total As contents: 49, 40, 29, 24, 18, 16 µg/L) were selected to remove As using agricultural by-products. Furthermore, four As solutions (200, 100, 50 and 25 µg/L) were prepared in the laboratory. Results revealed that corncobs and soybean hulls removed, respectively, 98% and 71% As from aqueous mediums after 120 min. Moreover, agricultural by-products were less effective in removing As from groundwater samples than synthetic solutions. The adsorption/removal capacity of by-products was lower at low initial As concentration compared to high initial levels, which needs further studies to explore the underlying mechanisms. Overall, the As removal efficiency of agriculture by-products differed significantly with respect to initial As level, contamination category, type of agricultural by-products and interaction duration. Therefore, these aspects need to be optimized before the possible use of an agricultural by-product as a potential biosorbent.

Risk assessment of trace element accumulation in soil and Brassica oleracea after wastewater irrigation.

The risk assessment of trace elements has received substantial attention for the achievement of UN Sustainable Developmental Goals (UN-SDGs). The present study aimed to evaluate health and ecological risks associated with trace element accumulation in Brassica oleracea under wastewater irrigations from three different areas. This study, for the first time, compared the pros and cons of mixed water crop irrigation (wastewater with fresh/groundwater). A pot experiment was conducted to evaluate the buildup of eight trace elements (As, Cu, Cd, Mn, Fe, Pb, Ni and Zn) in soil and B. oleracea plants irrigated with wastewater alone and mixed with fresh/groundwater. Specific ecological [degree of contamination (Cd), potential ecological risk index (PERI), pollution load index (PLI), geo-accumulation index (Igeo)], phytoaccumulation [bioconcentration factor (BCF) and transfer factor (TF)] and health risk models [chronic daily intake (CDI), hazard quotient (HQ), cancer risk (CR)] were applied to assess the overall contamination of trace elements in the soil-plant-human system. Moreover, these indices were compared with the literature data. The concentration of Cd, Fe and Mn exceeded the threshold limits of 10, 500 and 200 mg kg-1, respectively, for agricultural soil. Overall, all the irrigation waters caused significant pollution load in soil indicating high ecological risk (Cd > 24, PERI > 380, Igeo > 5, PLI > 2). Not all the mixing treatments caused a reduction in trace element buildup in soil. The mixing of wastewater-1 with either groundwater or freshwater increased trace element levels in the soil as well as risk indices compared to wastewater alone. The BCF and TF values were > 1, respectively, for 66% and 7% treatments. Trace element concentration in plants and associated health risk were minimized in mixed wastewater treatments. There were 22% and 32% reduction in HQ and CR when wastewater was mixed with freshwater and 29% and 8% when mixed with groundwater. Despite total reduction, a great variation in % change in risk indices was observed with respect to the area of wastewater collection. Therefore, mixed water irrigation may be a good management strategy, but its recommendation depends on soil properties and composition of waters used for mixing. Moreover, it is recommended that the freshwater and wastewater of the particular area may be continuously monitored to avoid potential associated health hazards.

A critical analysis of wastewater use in agriculture and associated health risks in Pakistan.

Freshwater shortage and its contamination with various types of pollutants are becoming the most alarming issues worldwide due to impacts on socioeconomic values. Considering an increasing freshwater scarcity, it is imperative for the growers, particularly in semiarid and arid areas, to use wastewater for crop production. Wastewaters generally contain numerous essential inorganic and organic nutrients which are considered necessary for plant metabolism. Besides, this practice provokes various hygienic, ecological and health concerns due to the occurrence of toxic substances such as heavy metals. Pakistan nowadays faces a severe freshwater scarcity. Consequently, untreated wastewater is used routinely in the agriculture sector. In this review, we have highlighted the negative and positive affectivity of wastewater on the chemical characteristics of the soil. This review critically delineates toxic metal accumulation in soil and their possible soil-plant-human transfer. We have also estimated and deliberated possible health hazards linked with the utilization of untreated city waste effluents for the cultivation of food/vegetable crops. Moreover, we carried out a multivariate analysis of data (144 studies of wastewater crop irrigation in Pakistan) to trace out common trends in published data. We have also compared the limit values of toxic metals in irrigation water, soil and plants. Furthermore, some viable solutions and future viewpoints are anticipated taking into account the on-ground situation in Pakistan-such as planning and sanitary matters, remedial/management technologies, awareness among local habitants (especially farmers) and the role of the government, NGOs and pertinent stakeholders. The data are supported by 13 tables and 7 figures.

Wound Healing Potential and In Silico Appraisal of Convolvulus arvensis L. Methanolic Extract.

Convolvulus arvensis L. is rich in phenolic compounds and traditionally used to treat wounds, skin ulcer, and inflammation. The current study is aimed at scientifically potentiating its traditional wound healing use. The methanolic extract of C. arvensis stem (CaME) was analyzed for HPLC and GC-MS analyses. The binding modes of active compounds were investigated against protein targets glycogen synthase kinase-3ß (GSK-3ß), transforming growth factor-beta (TGF-ß), c-myc, and ß-catenin by molecular docking followed by molecular dynamic simulations which revealed some conserved mode of binding as reported in crystal structures. The antioxidant potential of CaME was evaluated by in vitro methods such as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, hydrogen peroxide scavenging, and ferric reducing power assays. Ointment formulations of 10 and 20% CaME were applied topically and evaluated for wound healing potency against the excisional wound on the skin of Wistar rats. Gentamycin (0.1%) served as standard therapy. The healing process was observed for 20 days in the form of wound size and epithelialization followed by histopathological evaluation of the wound area. Chemical characterization showed the presence of 7-hexadecenoic acid, 2-hexadecylicosan-1-ol, quercetin, gallic acid, ferulic acid, and other compounds. The plant extract exhibited significant in vitro antioxidant activity. The animals treated with 10% ointment showed moderate healing, whereas the treatment with 20% CaME revealed healing potential comparable to the standard 0.1% gentamycin as coevidenced from histopathological evaluation of skin. The study corroborates promising potential of C. arvensis on the healing of wounds, which possibly will be attributed to its antioxidant activity, fatty acids, quercetin, and gallic and caffeic acids, and binding potential of its phytoconstituents (phenolic acids) with wound healing targets.

Body composition profiling and obesity analysis of healthy adults: A cross-sectional study.

Obesity as depicted by changes in the body composition is considered a global epidemic of the 21st century, predisposing to cardiometabolic diseases. This analytical cross-sectional study evaluated body composition parameters in both genders and conducted an obesity analysis of healthy adult Pakistani population. Using non-probability purposive sampling technique, data was collected from 205 healthy adults (aged 18-45 years), who had not been participating in any structured exercise or dietary regime over the last six months. Body composition was assessed using bioelectrical impedance analyser. For data analysis, descriptive statistics, Mann-Whitney U-test and one-sample T-test were applied. The mean body mass index was 24.3±4.93 kg/m2. Body composition components which were significantly higher in males included soft lean mass, fat-free mass index, skeletal muscle mass index and bone mineral content, whereas females had significantly higher percentage of body fat (PBF), visceral fat area and fat mass index (p<0.05). For obesity analysis, the mean PBF (34.61±9.68%) of our sample was higher than White, Hispanics and European adults. Majority of healthy adults had greater body fat mass and lower skeletal muscle mass. The primary obesity index was significantly higher in Pakistani population compared to other ethnicities, with females exhibiting a higher trend towards obesity.