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1.
bioRxiv ; 2024 May 05.
Article En | MEDLINE | ID: mdl-38746313

Schwann cells are vital to development and maintenance of the peripheral nervous system and their dysfunction has been implicated in a range of neurological and neoplastic disorders, including NF2 -related schwannomatosis. We have developed a novel human induced pluripotent stem cell (hiPSC) model for the study of Schwann cell differentiation in health and disease. We performed transcriptomic, immunofluorescence, and morphological analysis of hiPSC derived Schwann cell precursors (SPCs) and terminally differentiated Schwann-like cells (SLCs) representing distinct stages of development. To further validate our findings, we performed integrated, cross-species analyses across multiple external datasets at bulk and single cell resolution. Our hiPSC model of Schwann cell development shared overlapping gene expression signatures with human amniotic mesenchymal stem cell (hAMSCs) derived SLCs and in vivo mouse models, but also revealed unique features that may reflect species-specific aspects of Schwann cell biology. Moreover, we have identified gene co-expression modules that are dynamically regulated during hiPSC to SLC differentiation associated with ear and neural development, cell fate determination, the NF2 gene, and extracellular matrix (ECM) organization. By cross-referencing results between multiple datasets and analyses, we have identified potential new genes that are related to NF2 for further study including: ANXA1, CDH6, COL1A1, COL8A1, MFAP5, IGFBP5, FGF1, AHNAK, CDKN2B, LOX, CAV1 , and CAV2 . Our hiPSC model further provides a tractable platform for studying Schwann cell development in the context of human disease.

2.
ACS Omega ; 9(15): 17143-17153, 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38645361

Honey is a natural product produced by honeybees, which has been used not only as food but also as a medicine by humans for thousands of years. In this study, 60 kDa protein was purified from Pakistani Sidr honey named as SHP-60 (Sidr Honey Protein-60), and its antioxidant potential and the effect of Bevacizumab with purified protein on in vitro angiogenesis using human umbilical vein endothelial cells (HUVEC) were investigated. We further validated the molecular protein-protein (SHP-60 with Bevacizumab) interactions through in silico analysis. It showed very promising antioxidant activity by reducing 2,2-diphenyl-1-picrylhydrazyl free radicals with a maximum of 83% inhibition at 50 µM and an IC50 of 26.45 µM statistically significant (**p < 0.01). Angiogenesis is considered a hallmark of cancer, and without it, the tumor cannot grow or metastasize. Bevacizumab, SHP-60, and both in combination were used to treat HUVEC, and the MTT assay was used to assess cell viability. To demonstrate in vitro angiogenesis, HUVEC was grown on Geltrex, and the formation of endotubes was examined using a tube formation assay. HUVEC viability was dose-dependently decreased by Bevacizumab, SHP-60, and both together. Bevacizumab and SHP-60 both inhibited angiogenesis in vitro, and their combination displayed levels of inhibition even higher than those of Bevacizumab alone. We investigated the protein-protein molecular docking interactions and molecular dynamics simulation analysis of MRJP3 (major royal jelly protein 3) similar to SHP-60 in molecular weight with both the heavy chain (HC) and light chain (LC) of Bevacizumab. We found significant interactions between the LC and MRJP3, indicating that ASN468, GLN470, and ASN473 of MRJP3 interact with SER156, SER159, and GLU161 of LC of Bevacizumab. The integration of experimental data and computational techniques is believed to improve the reliability of the findings and aid in future drug design.

3.
Sci Total Environ ; 926: 171964, 2024 May 20.
Article En | MEDLINE | ID: mdl-38537810

Short (SCCPs) and medium (MCCPs) chain chlorinated paraffins being the emerging organic pollutants have raised serious concerns due to their widespread use and related human health risks. However, their occurrence in aquatic bodies like rivers and associated damage to ecological integrity is yet unknown in some regions of the world. The current study is the first ever assessment of SCCPs and MCCPs in sediment and water of river Ravi, Pakistan. Spatial occurrence and associated ecological risks were investigated from sediments (n = 16) and composite water samples (n = 8) collected at eight locations along the stretch of river Ravi. The concentrations of SCCPs and MCCPs varied from below limit of detection (

Chlorine , Hydrocarbons, Chlorinated , Humans , Animals , Hydrocarbons, Chlorinated/analysis , Paraffin/analysis , Rivers , Pakistan , Environmental Monitoring , Risk Assessment , Carbon , China
4.
Heliyon ; 10(5): e25757, 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38434385

The creation and manipulation of synthetic images have evolved rapidly, causing serious concerns about their effects on society. Although there have been various attempts to identify deep fake videos, these approaches are not universal. Identifying these misleading deepfakes is the first step in preventing them from spreading on social media sites. We introduce a unique deep-learning technique to identify fraudulent clips. Most deepfake identifiers currently focus on identifying face exchange, lip synchronous, expression modification, puppeteers, and other factors. However, exploring a consistent basis for all forms of fake videos and images in real-time forensics is challenging. We propose a hybrid technique that takes input from videos of successive targeted frames, then feeds these frames to the ResNet-Swish-BiLSTM, an optimized convolutional BiLSTM-based residual network for training and classification. This proposed method helps identify artifacts in deepfake images that do not seem real. To assess the robustness of our proposed model, we used the open deepfake detection challenge dataset (DFDC) and Face Forensics deepfake collections (FF++). We achieved 96.23% accuracy when using the FF++ digital record. In contrast, we attained 78.33% accuracy using the aggregated records from FF++ and DFDC. We performed extensive experiments and believe that our proposed method provides more significant results than existing techniques.

5.
Bioorg Chem ; 145: 107254, 2024 Apr.
Article En | MEDLINE | ID: mdl-38432152

Vanillic acid (VA) - a naturally occurring phenolic compound in plants - is not only used as a flavoring agent but also a prominent metabolite post tea consumption. VA and its associated compounds are believed to play a significant role in preventing diseases, underscoring the need for a systematic investigation. Herein, we report a 4-step synthesis employing the classical organic reactions, such as Willamson's alkylation, Fischer-Spier reaction, and Steglich esterification, complemented with a protection-deprotection strategy to prepare 46 VA derivatives across the five series (1a-1i, 2a-2i, 3, 3a-3i, 4a-4i, 5a-5i) in high yields. The synthesized compounds were investigated for their antifungal, anti-inflammatory, and toxic effects. Notably, compound 1a demonstrated remarkable ROS inhibition with an IC50 value of 5.1 ± 0.7 µg/mL, which is more than twice as effective as the standard ibuprofen drug. A subset of the synthesized derivatives (2b, 2c, 2e, 3b-3d, 4a-4c, 5a, and 5e) manifested their antifungal effect against drug-resistant Candida strains. Compound 5g, in particular, revealed synergism with the established antifungal drugs amphotericin B (AMB) and fluconazole (FLZ), doubling FLZ's potency against azole resistant Candida albican ATCC 36082. Furthermore, 5g improved the potency of these antifungals against FLZ-sensitive strains, including C. glabrata ATCC 2001 and C. parapsilosis ATCC 22019, as well as various multidrug-resistant (MDR) Candida strains, namely C. albicans ATCC 14053, C. albicans CL1, and C. krusei SH2L OM341600. Additionally, pharmacodynamics of compound 5g was examined using time-kill assay, and a benign safety profile was observed with no hemolytic activity in whole blood, and no cytotoxicity towards the normal BJ human cell line. The synergistic potential of 5g was further investigated through both experimental methods and docking simulations.These findings highlight the therapeutic potential of VA derivatives, particularly in addressing inflammation and circumventing FLZ resistance in Candida albicans.


Antifungal Agents , Mycoses , Humans , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Vanillic Acid/pharmacology , Vanillic Acid/therapeutic use , Azoles/pharmacology , Microbial Sensitivity Tests , Mycoses/drug therapy , Fluconazole/pharmacology , Candida , Candida albicans , Candida glabrata , Inflammation/drug therapy
6.
Diabetes Metab Syndr Obes ; 17: 675-689, 2024.
Article En | MEDLINE | ID: mdl-38352234

Purpose: To investigate the intestinal inflammatory response and the abundance of intestinal bacteria in rats with high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) and assess the intervention effects of taurine (TAU). Methods: Forty male Sprague-Dawley rats were randomly divided into five groups: group I, normal diet and normal saline gavage; group II, normal diet and TAU gavage; group III, HFD and normal saline gavage; group IV, HFD and TAU gavage (from the 1st week); group V, HFD and TAU gavage (from the 10th week). At the end of the 16th week, all the animals were sacrificed. Body weight, liver weight, liver function, and serum lipid levels were measured. The histopathologies of the liver and ileum were observed. The mRNA and protein expression levels of interleukin 17 (IL-17) and IL-10 in the ileum were detected by reverse transcription quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Three types of bacteria were detected in intestinal feces using the 16S rDNA qPCR method. Results: The ileal IL-17 level in group III was significantly higher than those in the other four groups (P < 0.01). The ileal IL-10 mRNA levels in group IV was significantly higher than those in groups III and V (P < 0.05), and IL-10 protein MOD levels in group III was significantly lower than those in the other four groups (P < 0.01). The numbers of Lactobacillus in group III were significantly lower than those in the other four groups (P < 0.01 or P < 0.05). The numbers of Bifidobacteria in groups IV and V were significantly increased compared with that in group III (P < 0.05). Conclusion: TAU may down-regulate the expression of IL-17, up-regulate the expression of IL-10 and regulate the intestinal flora, and alleviate the liver and intestinal damage in rats with HFD-induced NAFLD.

7.
Environ Res ; 249: 118435, 2024 May 15.
Article En | MEDLINE | ID: mdl-38350545

Rapid urbanization and associated waste generation have become a mounting ecological concern for wildlife, especially avian communities. Research has primarily focused on investigating the impacts of human activities on marine birds with comparatively less focus on terrestrial species that live in far more anthropized environments and are at significant risk. Our study has explored the abundance and characteristics of anthropogenic litter in 70 nests of four generalist bird species: Bank Myna (Acridotheres ginginianus), Common Myna (Acridotheres tristis), Black Kite (Milvus migrans) and House Crow (Corvus splendens), within the city of Lahore (Pakistan) and its surroundings, by determining and following an urbanization gradient. The overall frequency of litter occurrence (FLO%) for all the sampled nests was 89%. Over 80% of the recorded litter items consisted of plastic materials, primarily dominated by sheet-like plastics. There was a strong association between fabric and Black Kite nests, and metal and House Crow nests. Litter incorporation increased across the gradient from rural to urban habitats. The highest FLO% was found in nests sampled from waste dumping sites and urban sites (95%-100%), where anthropogenic influence was more intense. The high level of litter incorporation is potentially indicative of a species' adaptive response to urbanization, associated with the decline in natural nesting material and availability of anthropogenic litter. These findings highlight the need for strengthening the existing global database for terrestrial litter and its effect on wildlife and devising policy actions for better waste management and conservation of natural ecosystem balance.


Nesting Behavior , Urbanization , Animals , Pakistan , Birds/physiology , Anthropogenic Effects , Environmental Monitoring , Waste Products/analysis
8.
Heliyon ; 10(3): e25110, 2024 Feb 15.
Article En | MEDLINE | ID: mdl-38322973

Rice is a major source of carbohydrates worldwide. As the global population increases, its annual consumption also increases. Using the high-quality seeds, rice productivity can be enhanced. However, increasing seed access and availability is a major concern. This study aimed to map rice seed production and distribution in Indonesia and determine the challenges. It was carried out in 10 provinces in Indonesia from May to December 2022. These provinces are the centers of rice production in Indonesia. Primary (survey, focus group discussion, and key informant interviews) and secondary data collection methods were used. Results showed that producer capacity and production are closely related to institutional type, where legal institutions are more powerful in terms of knowledge, competency, and market. Almost all seed producers produced the extension seed class. The specific locations, agroecology, and rice consumer preferences affected the variety produced. Seeds were produced with good management, as shown by the adequacy of information types and sources. Furthermore, a free market is a sustainable strategy for selling seeds. The main challenges for seed rice production and distribution in Indonesia include encouraging appropriate resource management and planning (human, infrastructure, and financial) in the seed sector and increasing the linkage of seed stakeholders, such as research institutions, seed certification agencies, producers, and the government. A rapid and appropriate response to these challenges can increase seed availability for producers.

9.
Sci Rep ; 13(1): 19252, 2023 11 07.
Article En | MEDLINE | ID: mdl-37935763

Motorbike spoke wheel injuries (SWIs) among children are a notable public health concern, especially in low and middle-income regions. The primary objective of this study is to comprehensively examine the patterns of motorbike spoke wheel injuries (SWIs) in children. Additionally, the study introduces a novel classification system for these injuries. The implementation of this classification system aims to streamline the management of SWIs, making it more efficient and facilitating the development of standardized treatment protocols. This prospective observational study was conducted in the Accident and Emergency Department from January 2019 to 2021. Children < 14 years of age of either gender with foot and ankle injury due to motorbike spoke wheels as passengers and presenting within 3 days were included. The motorbike SWI was assessed for its location and classified by a new classification as Class I, Soft tissue injury without skin loss; Class II, Skin loss of more than 1 cm without underlying tissue involvement; Class III, Skin loss with underlying tissue involvement, this class is further divided on basis of underlying soft-tissue involvement; Class IV: mangled foot/toe. Management plan and outcome were noted. In our study158 children suffering from SWI were registered with a mean age of 6.2 ± 5.4 years, 127 (80.37%) males and 31 (19.62%) females. Class I injury was seen in 18 (11.39%) patients, class II in 69 (43.67%), and class III in 68 (43.03%) patients. Class III injuries were further subcategorized as follows: IIIT (Tendon) injuries, which accounted for 32 cases (20.25%); IIIB (Bone) injuries, with 29 cases (18.35%); and IIINV (Neurovascular) injuries, identified in 7 cases (4.43%). Class IV injuries were observed in 3 (1.8%) children. The flap was needed in 33 (20.88%) patients. There were no complications like flap necrosis or graft rejection. In this current study, a new classification system specific for a motorbike SWI has been introduced along with its application on children presenting at tertiary care hospital's emergency department. The application of the proposed classification will enable universal management guidelines for SWIs, especially in the Ino-Pak region where SWIs are common.


Ankle Injuries , Musculoskeletal System , Soft Tissue Injuries , Child , Child, Preschool , Female , Humans , Infant , Male , Ankle Injuries/surgery , Developing Countries , Motorcycles , Musculoskeletal System/surgery , Skin Transplantation/methods , Soft Tissue Injuries/surgery , Surgical Flaps/surgery , Treatment Outcome
10.
Pak J Pharm Sci ; 36(2): 501-506, 2023 Mar.
Article En | MEDLINE | ID: mdl-37530158

Lung cancer is the most typical form of cancer that results in death worldwide. Patients with non-small cell lung cancer (NSCLC) have an around 15% survival rate despite of advancement in cancer treatment. This study aimed to evaluate the combined effect of celecoxib and bevacizumab on NSCLC using A549 cells as an in vitro model. The A549 cells were culture and treated with celecoxib, bevacizumab and their combination and the cell proliferation was assessed using MTT assay, whereas cell apoptosis was analyzed using flowcytometry. The effects on the apoptotic genes were examined using western blotting, while qPCR was used for analyzing the VEGF and MMP-9 expression. Celecoxib, bevacizumab and their combination exhibited a dose dependent inhibition (p<0.001). The rate of apoptosis was 14.1% and 26.5% but when the two drugs were combined, the rate of apoptosis was significantly increased due to synergism by 52.2% (p<0.001). Western blotting displayed that co-treatment significantly up regulated proapoptotic genes (caspase-3 and -9) and down regulated anti-apoptotic gene (Bcl-2) (p<0.001). Additionally, VEGF and MMP-9 expression were both significantly reduced with co-treatment compared to the control (p<0.001). Celecoxib combined with bevacizumab synergistically inhibited NSCLC by inducing apoptosis and modulating VEGF and MMP-9 expression.


Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Celecoxib/pharmacology , Celecoxib/therapeutic use , Lung Neoplasms/genetics , Bevacizumab/pharmacology , Bevacizumab/therapeutic use , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/pharmacology , Matrix Metalloproteinase 9/genetics , Cell Line, Tumor , Apoptosis , Cell Proliferation
12.
Case Rep Neurol ; 15(1): 131-139, 2023.
Article En | MEDLINE | ID: mdl-37483461

COVID-19 is a novel virus which causes a variety of clinical manifestations in the body, some of which are yet to be discovered. The main aim of our study is to highlight the neurological manifestations of COVID-19 as it is still new to the medical world, and to emphasize the fact that the physicians have to be wary of the possibility that patients affected by COVID-19 can present with encephalitis. Only a few studies are available so far regarding the neurological manifestations of this novel virus which highlights the need for this study. We present a case series of 4 patients who were found to have COVID-19 encephalitis. There is still no disease-defining test for diagnosis so the mainstay of diagnosis is exclusion of all the common causes of encephalitis. Brain magnetic resonance imaging and cerebrospinal fluid analysis performs an ancillary in the diagnostic tools. Our study also supports the use of IV tocilizumab (4-8 mg/kg) and IV methylprednisolone (0.5-2 mg/kg) as possible treatment options with good results, as the patients described in our case series responded well to these medications.

13.
J AOAC Int ; 106(5): 1180-1189, 2023 Sep 01.
Article En | MEDLINE | ID: mdl-37307094

BACKGROUND: Linezolid (LNZ) is extremely prone to resistance. The development of resistance to LNZ should be taken into consideration when selecting this drug as a therapeutic option. It is well established that reactive oxygen species (ROS) generated by iron oxide nanoparticles (MNPs) could kill the infecting bacteria. So, we hypothesized the synergistic antibacterial effect of iron oxide nanoparticles and LNZ. OBJECTIVE: To study the release and antibacterial effects of LNZ-loaded superparamagnetic iron oxide nanoparticles (SPIONs) on Staphylococcus aureus and Streptococcus pneumoniae. METHOD: Ferrofluid containing SPIONs was synthesized via chemical co-precipitation method and stabilized by sodium lauryl sulphate (SLS). SPIONs were then loaded with LNZ and characterized for particle size, FT-IR, XRD, and entrapment efficiency. Further antibacterial activity of SPIONs and LNZ-loaded SPIONs was investigated. For the in vitro release findings, HPLC analytical method development and validation were performed. RESULTS: Isolation of LNZ was accomplished on a C-18 column with methanol-TBHS (tetra butyl ammonium hydrogen sulphate, 50:50, v/v). The eluate was monitored at 247 nm with a retention time of 4.175 min. The MNP's DLS measurement revealed monodispersed particles with an average size of 16.81 ± 1.07 nm and PDI 0.176 ± 0.012. In optimized formulation, 25 ± 1.75% (w/w) of the drug was found to be entrapped. XRD revealed uniform coating of oleic acid covering the entire magnetic particles' surface with no change in its crystallinity. An effective antimicrobial activity was observed at the lowered dose of drug. CONCLUSIONS: A robust HPLC method was developed to quantify the LNZ in MNPs, and outcomes showed that the reduced dose of LNZ incorporated in SPIONs was able to show similar activity as the marketed product. HIGHLIGHTS: Successfully reduction of the dose of LNZ was established with the aid of biocompatible MNPs to attain the equivalent antibacterial activity.


Anti-Bacterial Agents , Magnetite Nanoparticles , Linezolid/pharmacology , Chromatography, High Pressure Liquid , Spectroscopy, Fourier Transform Infrared , Anti-Bacterial Agents/pharmacology , Magnetic Iron Oxide Nanoparticles , Magnetite Nanoparticles/chemistry
14.
J Cosmet Dermatol ; 22(10): 2839-2851, 2023 Oct.
Article En | MEDLINE | ID: mdl-37309263

BACKGROUND: Ursolic acid is a powerful drug that possesses many therapeutic properties, such as hepatoprotection, immunomodulation, anti-inflammatory, antidiabetic, antibacterial, antiviral, antiulcer, and anticancer activity. Centella asiatica (L.) Urban (Umbelliferae) contains a triterpene called asiatic acid, which has been used effectively in traditional Chinese and Indian medicine system for centuries. Anticancer, anti-inflammatory, and neuroprotective properties are only some of the many pharmacological actions previously attributed to asiatic acid . AIM: The present work developed an optimized combinatorial drug-loaded nano-formulation by Quality by design approach. MATERIALS AND METHODS: The optimize transliposome for accentuated dermal delivery of dual drug. The optimization of drug-loaded transliposome was done using the "Box-Behnken design." The optimized formulation was characterized for vesicles size, entrapment efficiency (%), and in vitro drug release. Additionally, transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), and dermatokinetic study were performed for further evaluation of drug-loaded optimized transliposome formulation. RESULTS: The optimized combinatorial drug-loaded transliposome formulation showed a particle size of 86.36 ± 2.54 nm, polydispersity index (PDI) 0.230 ± 0.008, and an entrapment efficiency of 87.43 ± 2.66% which depicted good entrapment efficiency. In vitro drug release of ursolic acid and asiatic acid transliposomes was found to be 85.12 ± 2.54% and 80.23 ± 3.23%, respectively, as compared to optimized ursolic acid and asiatic acid transliposome gel drug release that was 67.18 ± 2.85% and 60.28 ± 4.12%, respectively. The skin permeation study of ursolic and asiatic acid conventional formulation was only 32.48 ± 2.42%, compared with optimized combinatorial drug-loaded transliposome gel (79.83 ± 4.52%) at 12 h. After applying combinatorial drug-loaded transliposome gel, rhodamine was able to more easily cross rat skin, as observed by confocal laser scanning microscopy, in comparison with when the rhodamine control solution was used. DISCUSSION: The UA_AA-TL gel formulation absorbed more ursolic acid and asiatic acid than the UA_AA-CF gel formulation, as per dermatokinetic study. Even after being incorporated into transliposome vesicles, the antioxidant effects of ursolic and asiatic acid were still detectable. In most cases, transliposomes vesicular systems generate depots in the skin's deeper layers and gradually release the medicine over time, allowing for fewer applications. CONCLUSION: In overall our studies, it may be concluded that developed dual drug-loaded transliposomal formulation has great potential for effective topical drug delivery for skin cancer.


Drug Carriers , Skin Absorption , Rats , Animals , Administration, Cutaneous , Drug Carriers/pharmacology , Skin , Drug Delivery Systems , Rhodamines/metabolism , Rhodamines/pharmacology , Particle Size , Ursolic Acid
15.
Environ Monit Assess ; 195(6): 638, 2023 May 03.
Article En | MEDLINE | ID: mdl-37138178

The present study aimed to find out the source, distribution, quantity, and incipient threats of the microplastics (MPs) released by food-packing plastic materials, plastic bags, bottles, and containers on human health, biodiversity, water bodies, and atmosphere. For this purpose, 152 articles about MPs (0.1 to 5000 µm) and nanoplastics (NP) 1 to 100 nm) were reviewed and interpreted their results in the present articles about microplastics. The highest plastic waste is generated by China (⁓ 59 Mt), the USA (⁓ 38 Mt), Brazil (⁓ 12 Mt), Germany (⁓ 15 Mt), and Pakistan (⁓ 6 Mt). The count of MPs (MPs/kg) in Chinese salt was 718, UK 136, Iran 48, and USA 32, while MPs in bivalves, i.e., in Chinese bivalves was 2.93, UK 2.9, Iran 2.2, and Italy 7.2 in MPs/kg, respectively. The MPs count in Chinese fish was 7.3, Italy's 23, the USA's 13, and UK's 1.25 in MPs/kg, respectively. The MP concentrations in the water bodies, i.e., USA, were 15.2, Italy 7, and UK 4.4 in mg/L, respectively. It was critically reviewed that MPs can enter the human body causing various disorders (neurotoxic, biotoxic, mutagenic, teratogenic, and carcinogenic disorders) because of the presence of various polymers. The present study concluded that MPs were released from processed and stored food containers, either through physical, biological, or chemical means, which harshly affect the surrounding environment and human health. The study recommended that alternatives to plastic containers are glass and bioplastic containers, papers, cotton bags, wooden boxes, and tree leaves need to use to avoid direct consumption of MPs from food.


Plastics , Water Pollutants, Chemical , Animals , Humans , Plastics/analysis , Microplastics/analysis , Food Storage , Environmental Monitoring/methods , Water Pollutants, Chemical/analysis , Water
16.
J Taibah Univ Med Sci ; 18(5): 1011-1017, 2023 Oct.
Article En | MEDLINE | ID: mdl-36959917

Objective: Angiogenesis plays an important role in various physiological and pathological conditions and is essential for tumor growth and metastasis. The aim of this study was to evaluate the effect of a combination of vandetanib and celecoxib on angiogenic tube formation and its effect on angiogenic genes (MMP-2 and MMP-9) using an in vitro model of human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were cultured and verified by flow cytometry. HUVECs were then treated with vandetanib, celecoxib, and the combination of both drugs. Then, we investigated cell viability and cell apoptosis by MTT assays and flow cytometry. The process of angiogenesis was analyzed by tube formation assays, and the effect on angiogenic genes was determined by RT-qPCR. Results: HUVECs were positive for CD144 and negative for CD14. Vandetanib, celecoxib, and their combination inhibited HUVEC viability in a dose-dependent manner (p < 0.001). The rate of apoptosis was 13.1%, 9%, and 23.7% (p < 0.001) when treated with vandetanib, celecoxib, or the combination of both drugs, respectively. Vandetanib inhibited tube formation by 43.7%, celecoxib by 21%, and their combination by 77.3% (p < 0.001), respectively. RT-qPCR revealed that both vandetanib and celecoxib reduced the expression levels of MMP-2 and MMP-9, and their combination resulted in an even greater extent of reduction in expression levels (p < 0.001). Conclusion: Celecoxib enhanced the effect of vandetanib in inhibiting in vitro angiogenesis and the combination of these two drugs led to even greater extents of inhibition than vandetanib alone.

17.
Environ Toxicol Chem ; 42(3): 727-739, 2023 03.
Article En | MEDLINE | ID: mdl-36636893

The presence of microplastics in different environmental matrices has raised many concerns about potential effects of microplastics on humans and freshwater ecosystems. In Pakistan, rivers potentially receive microplastics from anthropogenic activities in their catchments. However, research studies regarding microplastics' presence, distribution, and risks are scarce in Pakistan. To bridge the gap, the present study was conducted to evaluate microplastic pollution in the Chenab River. Surface water samples were collected from selected sites on the Chenab River using a manta trawl in the low-flow season during postmonsoon (October) 2019 and 2020 and in the high-flow season during monsoon (July) 2020 and 2021. Samples were digested, followed by density separation and filtration. Identification and polymer characterization of microplastics were completed using stereomicroscopy and attenuated total reflection Fourier transform infrared spectroscopy, respectively. Microplastics were found in all samples with significant spatiotemporal variation in microplastic concentration, with an average of 45.98 ± 10.45 microplastics/m3 in the low-flow season and 34.66 ± 16.15 microplastics/m3 in the high-flow season. Among microplastic shapes, fibers were the most dominant shape, whereas polyethylene terephthalate (38.2%) and polypropylene (19%) were the most abundant polymers. Polymer risk index analysis and pollution load index demonstrated that most of the sites ranked as safe. The potential ecological risks from single polymers and combined polymers showed minor risks posed by microplastics. The present study is the first step to focus on microplastic pollution in the Chenab River; it will help river managers to mitigate the microplastic pollution without compromising the ecological integrity of the river. Environ Toxicol Chem 2023;42:727-739. © 2023 SETAC.


Microplastics , Water Pollutants, Chemical , Humans , Microplastics/analysis , Plastics/analysis , Rivers/chemistry , Ecosystem , Water Pollutants, Chemical/analysis , Environmental Monitoring/methods , Polymers
18.
Eur J Orthop Surg Traumatol ; 33(5): 1767-1772, 2023 Jul.
Article En | MEDLINE | ID: mdl-35947197

BACKGROUND: Review of the published articles does not show any study done to see if children with torus fracture are with Vitamin D deficiency. The aim of this study was to determine association of inadequacy of Vitamin D level with torus fracture and its predictors in children in Karachi Pakistan. METHODS: Patient underage of 13 years came with torus fracture were included in study, and managed non-operatively with below elbow cast. Proforma was made which includes demographic data (age, gender, nutritional status) and exposure to sunlight, dietary habits, kind to apparel and type of accommodation they were living at. All participants underwent measurement of serum vitamin D level. RESULTS: Out of 558 children presented with limb fractures in emergency department, 190 (34.05%) had torus fracture, with mean age of 6.0 ± 4.2 years. 93 (48.94%) in pre-school group, 59 (31.05%) in school and 38 (20%) were breast-fed. On nutritional status, malnourished were 72 (37.89%), out of which 32 (44.44%) had first-degree malnutrition. On vitamin D level status only 52 (27.36%) participants had Vitamin D within normal range while 86 (45.26%) were found Vitamin D deficient. We found that vitamin D level is directly related to nutritional status, duration of sun exposure maternal vitamin d levels and not significantly related to age, gender, type of accommodation and different fabric types. CONCLUSION: In this study torus fracture in children is significantly associated with Vitamin D deficiency, with common predictors including nutritional status, maternal Vitamin D level for lactating mothers and duration of exposure of sunlight. Vitamin D supplementation in children can prevent a significant number of fractures via national programs for food fortification and increase the awareness of general population on the importance of sunlight exposure and intake of food rich in Vitamin D.


Fractures, Bone , Vitamin D Deficiency , Female , Humans , Child , Child, Preschool , Infant , Vitamin D , Lactation , Prevalence , Vitamin D Deficiency/complications , Vitamin D Deficiency/epidemiology , Vitamins , Fractures, Bone/etiology , Fractures, Bone/complications
19.
Environ Sci Pollut Res Int ; 30(1): 727-738, 2023 Jan.
Article En | MEDLINE | ID: mdl-35906523

Microplastics (MP) pollution is an emerging threat to life and the environment. These particles are not restricted to human-inhabited lands but also found in different mountains and glaciers where the human population is relatively low. These MPs make their way to the river ecosystem from glaciers, rains, and municipal and industrial effluents. The current study was designed to highlight MPs' pollution in water, sediments, and fishes of the Swat River: originating from the Hindu Kush Mountain Range. These samples were collected from eight different sites across the river. An average concentration of MPs detected in water samples (305.79 ± 289.66 MPs/m3), fish (12.54 ± 8.02 MPs/individual), and sediments (588.29 ± 253.95 MPs/kg). The highest concentration was observed among water samples at Mingora city and the lowest at the confluence point of the rivers near Charsadda being 753.71 ± 330.08 MPs/m3 and 57.64 ± 31.98 MPs/m3, respectively. MP concentrations in the sediment samples were also the highest at Mingora city (834.0 ± 367.21 MPs/kg), and lowest at Chakdara (215.0 ± 20.0 MPs/kg). Among the fish samples, Schizothorax plagiostomus contained the highest while Wallago attu contained the lowest MP concentrations corresponding to 17.08 ± 8.27 MPs/individual and 5.0 ± 2.36 MPs/individual, respectively. Fibers were the most prevalent MPs in all the matrices representing 80%, 92%, and 85% of the total MP count in water, sediments, and fish samples. These findings highlighted that freshwater ecosystem are not free from MPs and are as much vulnerable to anthropogenic activities as marine ecosystem. Therefore, need attention not less than marine ecosystem awareness, education, ecotourism, sustainable reduction in plastic use, and strict rules and regulations could be helpful to prevent the anthropogenic menace.


Catfishes , Water Pollutants, Chemical , Animals , Humans , Microplastics , Plastics , Rivers , Water , Ecosystem , Pakistan , Geologic Sediments , Water Pollutants, Chemical/analysis , Environmental Monitoring
20.
Environ Sci Pollut Res Int ; 30(5): 12965-12978, 2023 Jan.
Article En | MEDLINE | ID: mdl-36121631

Punjab is the leading province of Pakistan in the production of bovine milk and its consumption. Rapid industrialization, high energy demand, and the production of waste have increased the risk of polychlorinated biphenyls (PCBs) toxicity in the environment. This research work was designed to assess human dietary exposure of ∑PCBs17 congeners through ingestion of buffalo and cow's milk from eight main districts of Punjab, Pakistan. The average concentrations of ∑DL-PCBs (8.74 ng g-1 and 14.60 ng g-1) and ∑I-PCBs (11.54 ng g-1 and 18.68 ng g-1) in buffalo and cow milk samples were analyzed, respectively. The PCB-156 was predominantly high congener found in both buffalo (2.84 ng g-1) and cow milk (2.86 ng g-1). It was found that the highest PCBs in bovine milk samples were observed in close vicinities of urban and industrial areas. The estimated daily consumptions of DL-PCBs and I-PCBs, from buffalo and cow milk, were below the acceptable daily intake for both adults and children. Moreover, hazard quotients (HQ) of the ∑PCBs17 congener value were less than 1.0 in adults and greater in the case of children reflecting the high chances of cancer. Furthermore, comprehensive monitoring for childhood cancer is recommended to establish the relationship in future studies.


Milk , Polychlorinated Biphenyls , Adult , Child , Female , Animals , Cattle , Humans , Milk/chemistry , Polychlorinated Biphenyls/analysis , Pakistan , Buffaloes , Milk, Human/chemistry
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