Diagnostic Accuracy of Immunohistochemical Expression of p16, MDM2, and CDK4 in Well-Differentiated and De-Differentiated Liposarcoma in MDM2 Fluorescent in situ Hybridisation Confirmed Cases.

OBJECTIVE: To establish the diagnostic utility of immunohistochemistry markers p16 along with MDM2 and CDK-4 in confirming the diagnosis of well-differentiated and de-differentiated liposarcoma while taking Fluorescent in situ Hybridisation (FISH) as a gold standard. STUDY DESIGN: A cross-sectional study. Place and Duration of the Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from 30th January 2022 to 30th June 2023. METHODOLOGY: A standard panel of three immunohistochemistry markers p16, MDM2, and CDK4 were applied to 36 cases of atypical lipomatous tumours, well-differentiated liposarcoma (WDLPS), and de-differentiated liposarcoma (DDLPS), on which the gold standard FISH was already performed. The sample size was calculated with the help of a WHO calculator taking prevalence 1-2% in Pakistani population. Qualitative variables such as gender and site of tumour were presented by calculating frequency and percentages and comparison of Immunohistochemistry results with FISH was done by using a 2x2 table. RESULTS: The sensitivity and specificity of this triple marker panel for detecting WDLPS/DDLPS were 43.47% and 15.38%, respectively. The sensitivity and specificity of CDK4 for detecting WDLPS / DDLPS were 82.6% and 15.4%, those of MDM2 were 73.9% and 61.5 %, and those of p16 were 60.9% and 53.8%, respectively. CONCLUSION: Among all three markers, CDK4 was the most sensitive and MDM2 was the most specific marker for detecting WDLPS-DDLPS. It also showed that a combination of these three markers improves the diagnostic credibility of the immunohistochemistry in diagnosing DDLPS and WDLPS but FISH is the most reliable and confirmatory method. KEY WORDS: De-differentiated liposarcoma, Well-differentiated liposarcoma, P16, CDK4, MDM2.

Profusion of microplastics in dental healthcare units; morphological, polymer, and seasonal trends with hazardous consequences for humans.

Given the convenience of using plastics, addressing the growing concerns about their hazardous health effects is imperative. Consequently, a comprehensive risk assessment is necessary to gauge the potential harm microplastics pose. With its urgent call to action, this study aimed to investigate the indoor source and abundance of microplastics in private dental units during routine professional activities. The current analyzed microplastic quantity variations based on morphological characteristics, seasonal fluctuations and polymer-types. The polymer hazard index (PHI) was calculated to evaluate the significant human health risks posed to dental professionals by inhalation of microplastics. Dust samples were collected using a clean brush and steel pan from various flat and horizontal surfaces within each dental unit. The study found that clinical dental units had fewer microplastics (587 ± 184.9 MPs/g/day) than teaching hospitals (1083.80 ± 133.7MPs/g/day), with comparatively more abundance in winter (31 %). ATR-FTIR analysis determined polyethylene terephthalate to be a more abundant polymer (39 %). This study also found an average inhalation microplastic intake risk of 20.23 MP/g/day and 5259.85 MP/g/year for clinical and 29.45 MP/g/day and 765.12 MP/g/year for teaching hospital dental units. Female dental professionals have 1.1 times more microplastic inhalation risks than male dental professionals. According to PHI findings, overall minor to medium polymer risk was determined. In conclusion, this evidence-based research underscores the urgent need for a shift towards more sustainable practices in the dental healthcare sector. Dental professionals should prioritize using non-plastic material protective equipment and a proper ventilation system to reduce exposure to these particles.

Source identification, characteristics, and spatial distribution of airborne microplastic deposition in Lahore City, Pakistan.

A large volume of atmospheric microplastics (MPs) has been observed worldwide and is considered an emerging global environmental issue. Nevertheless, no significant assessment of the atmospheric deposition of MPs in Pakistan has been reported yet. The present study was designed to highlight the source, type, and spatial distribution of MPs in atmospheric fallout in Lahore, Pakistan. A total of 23 sites were sampled in Lahore with a heterogeneous background of human activities. All samples were collected in a box with a one-foot depth fitted with a steel tray of 0.1 m2 at the bottom. Fenton's reagent and hydrogen peroxide were used to remove organic matter, and sodium chloride for density separation, while the MPs were quantified through a stereomicroscope, and polymers were identified through ATR-FTIR spectroscopy. The highest deposition rate (particles/m2/day) was observed at Badami Bagh, i.e., 6819, followed by Mall Road 4414, and Chung 4263, while the lowest was in Sabzazaar (i.e., 524) and Township (1047) with an average deposition rate of 2340 ± 1392. Among the MPs, the major portion was fiber, i.e., 96%, while fragment was 1.9%, sheets 0.78%, foams 1.12%, beads 0.04%, and other MPs 0.06%. At all sampling sites, 20 different types of polymers were identified with different percentages, of which polyester fibers were predominant with an abundance of 96.09% associated with clothes and textiles. A high frequency of MPs was found in populated areas with dense traffic, plastic wastes, household plastic materials, and mismanagement of wastes, which accelerates the atmospheric deposition of airborne microplastics. Evaluation and characterization of MP help assess health and environmental impacts, cleanup efforts, and guiding regulations. It also provides valuable information for waste management innovation to reduce plastic pollution.

Undiagnosed vertebral fragility fractures in patients with distal radius fragility fractures: an opportunity for prevention of morbimortality in osteoporotic patients in developing countries.

Our study investigates vertebral fractures in individuals with distal radius fractures. Among 512 patients, 41.21% had vertebral fractures, predominantly in the lumbar spine. These findings highlight the importance of screening for vertebral fractures in this population, informing early intervention strategies to mitigate risks associated with osteoporosis. PURPOSE: This study's main goal was to look into the frequency, location, kind, and severity of asymptomatic vertebral fragility fractures (VFF) in people who had fractures of the fragility of the distal radius. Although VFF is frequently misdiagnosed, it is linked to higher mortality, morbidity, and hip fracture risk. The study also attempted to investigate the relationship between VFF and certain demographic and lifestyle factors, as well as FRAX data, in this patient population. METHODS: Between January, 2021, and January, 2022, individuals with low-energy distal radial fractures who presented to the emergency room of tertiary care hospital of Karachi, Pakistan, were the subject of a cross-sectional study and were 45 years of age or older except those who fitted the exclusion criteria (n = 208). The thoracic and/or lumbar spine was imaged using radiology, and information on demographics, way of life, and FRAX (Fracture Risk Assessment Tool) was gathered. Using the Genant semiquantitative approach, an impartial and blinded orthopaedist identified VF in the images and determined their severity. SPSS version 20 was used to analyse the data. RESULTS: Two hundred eleven (41.21%) of them were found to have radiographic VFF and only 12 (2.34%) of the 512 patients who were tested were getting osteoporotic therapy. The thoracic spine (32.7%), followed by the lumbar spine (43.12%), was the area most frequently afflicted. In 24.17% of the patients, multiple fractures of the thoracolumbar spine were found. The wedge form (54.5%), followed by biconcave (30.81%) and crush (14.7%), was the most prevalent VFF type. The majority of detected VFF were rated as having a 25-40% height loss (64.9%) then severe (> 40%) fractures (35.1%), according to the Genant grading method. Notably, there were no variations in smoking, drinking, BMI, or FRAX score between patients with and without VFF that were statistically significant. CONCLUSION: Based on our study's findings, it is clear that osteoporotic vertebral fragility fractures occur in almost half of individuals with distal radius fractures. The lumbar spine is notably the most affected region, predominantly with wedge fractures. Given the high prevalence of asymptomatic vertebral fragility fractures (VFF), proactive measures are necessary to mitigate associated risks. Prioritising comprehensive fall risk assessments for these patients and interventions to enhance bone mineral density and strength are crucial. Early identification of asymptomatic VFF enables timely intervention, optimising patient care and minimising the risk of complications in this vulnerable population.

Temporal trends in indoor bioaerosols: implications for dental healthcare environments.

Antibiotic resistance, a significant public health hazard, is predicted to cause 10 million deaths worldwide by 2050. The study aimed to identify culturable bioaerosols in the indoor air of dental units in Lahore and assess their antibiotic resistance. Air samples were collected from 10 dental unit locations at different distances, with average concentrations of fungi and bacteria falling within intermediate ranges, per the Global Index of Microbial Contamination (GIMC/m3) index. The study found higher antibiotic-resistant strains in hospital dental units, particularly during winter. The most vigorous strain, S.aureus-NAJIH18, exhibited 70% resistance to ceftazidime. The research highlights the importance of quantifying microbial pollutants for evaluating their source and complexity. It suggests proactive mitigation techniques, such as focused cleaning and air filtration, to improve indoor air quality can mitigate the spread of antibiotic-resistant strains. These insights offer hope in combating the growing public health threat of antibiotic resistance.

A novel induced pluripotent stem cell model of Schwann cell differentiation reveals NF2 - related gene regulatory networks of the extracellular matrix.

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 developed a novel human induced pluripotent stem cell (hiPSC) model to study 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 cells (SCs) representing distinct stages of development. To 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 SCs and in vivo mouse models, but also revealed unique features that may reflect species-specific aspects of Schwann cell biology. Moreover, we identified gene co-expression modules that are dynamically regulated during hiPSC to SC 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, we identified new genes potentially associated with NF2 expression. Our hiPSC model further provides a tractable platform for studying Schwann cell development in the context of human disease.

Investigating the Protein-Based Therapeutic Relationship between Honey Protein SHP-60 and Bevacizumab on Angiogenesis: Exploring the Synergistic Effect through In Vitro and In Silico Analysis.

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.

Spatial distribution and ecological risk assessment of short and medium chain chlorinated paraffins in water and sediments of river Ravi, Pakistan.

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 (

Unleashing the potential of vanillic acid: A new twist on nature's recipe to fight inflammation and circumvent azole-resistant fungal infections.

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.

An efficient deepfake video detection using robust deep learning.

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.

Nesting material adaptation of native bird species with anthropogenic litter along an urbanization gradient in Pakistan.

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.

Commercial rice seed production and distribution in Indonesia.

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.

Taurine Regulates the Expression of Interleukin -17/10 and Intestinal Flora and Protects the Liver and Intestinal Mucosa in a Nonalcoholic Fatty Liver Disease Rat Model.

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.

Introducing the Muzzammil classification for spoke wheel injuries in children to enhance injury assessment and treatment in developing countries.

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.

Celecoxib and bevacizumab synergistically inhibit non-small cell lung cancer by inducing apoptosis and modulating VEGF and MMP-9 expression.

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.

Encephalitis as a Clinical Manifestation of COVID-19: A Case Series.

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.

Development and Antibacterial Investigation of Linezolid-Loaded SPIONs and HPLC Method Development for Quantitative Analysis of Linezolid.

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.

Combinatorial drug-loaded quality by design adapted transliposome gel formulation for dermal delivery: In vitro and dermatokinetic study.

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.

Sources, distribution, and incipient threats of polymeric microplastic released from food storage plastic materials.

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.