Consumption of ß-Caryophyllene Increases the Mating Success of Bactrocera zonata Males (Diptera: Tephritidae).

The peach fruit fly, Bactrocera zonata (Saunders) (Diptera: Tephritidae), is an economically important polyphagous quarantine pest of horticultural crops endemic to South and Southeast Asia. Methyl eugenol (ME), a naturally occurring phenylpropanoid, is a male attractant used to lure and (when mixed with an insecticide) annihilate the males from the wild population, a method of pest control termed the male annihilation technique (MAT). ME is reported to enhance the mating success of sterile males of Bactrocera spp., which is critical for enhancing the effectiveness of the sterile insect technique (SIT). The suppressed response of ME-treated males to ME-baited traps/devices allows the simultaneous application of the MAT and SIT, increasing the efficiency of area-wide integrated pest management (AW-IPM) programs. However, ME treatment in sterile males in SIT facilities is logistically difficult. ß-caryophyllene (BCP) is a widely occurring, safer plant compound and is considered suitable for treating males in SIT facilities. Here, we demonstrate that BCP feeding enhanced B. zonata male mating success to the same extent as ME feeding. Feeding on BCP suppressed the male's subsequent attraction to ME-baited traps, but not to the same degree as feeding on ME. The results are discussed and BCP is suggested as an alternative to ME for the concurrent use of the MAT and SIT.

Thiamethoxam-Induced Intergenerational Sublethal Effects on the Life History and Feeding Behavior of Rhopalosiphum padi.

Thiamethoxam, a second-generation neonicotinoid insecticide is widely used for controlling sap-sucking insect pests including Rhopalosiphum padi. The current study aimed to investigate the life-history parameters and feeding behavior of R. padi following treatments with sublethal concentrations of thiamethoxam. The lethal concentration 50 (LC50) value of thiamethoxam against adult R. padi was 11.458 mg L-1 after 48 h exposure. The sublethal concentrations of thiamethoxam (LC5 and LC10) significantly decreased the adult longevity, fecundity, and reproductive days in the directly exposed aphids (F0 generation). In the progeny R. padi (F1), the developmental durations and total prereproductive period (TPRP) were decreased while the adult longevity, fecundity, and reproductive days (RPd) were increased at both thiamethoxam concentrations. The demographic parameters including the net reproductive rate (R0), intrinsic rate of increase (r), and finite rate of increase (λ) were prolonged only at the LC5 of thiamethoxam. The EPG results indicated that the sublethal concentrations of thiamethoxam increases the total duration of non-probing (Np) while reducing the total duration of E2 in directly exposed aphids (F0). Interestingly, the E2 were significantly increased in the progeny generation (F1) descending from previously exposed parental aphids (F0). Overall, this study showed that thiamethoxam exhibited high toxicity against directly exposed individuals (F0), while inducing intergenerational hormetic effects on the progeny generation (F1) of R. padi. These findings provided crucial details about thiamethoxam-induced hormetic effects that might be useful in managing resurgences of this key pest.

Hormetic effects of thiamethoxam on Schizaphis graminum: demographics and feeding behavior.

In agroecosystems, insects contend with chemical insecticides often encountered at sublethal concentrations. Insects' exposure to these mild stresses may induce hormetic effects, which has consequences for managing insect pests. In this study, we used an electrical penetration graph (EPG) technique to investigate the feeding behavior and an age-stage, two-sex life table approach to estimate the sublethal effects of thiamethoxam on greenbug, Schizaphis graminum. The LC5 and LC10 of thiamethoxam significantly decreased longevity and fecundity of directly exposed adult aphids (F0). However, the adult longevity, fecundity, and reproductive days (RPd)-indicating the number of days in which the females produce offspring - in the progeny generation (F1) exhibited significant increase when parental aphids (F0) were treated with LC5 of the active ingredient. Subsequently, key demographic parameters such as intrinsic rate of increase (r) and net reproductive rate (R0) significantly increased at LC5 treatment. EPG recordings showed that total durations of non-probing (Np), intercellular stylet pathway (C), and salivary secretion into the sieve element (E1) were significantly increased, while mean duration of probing (Pr) and total duration of phloem sap ingestion and concurrent salivation (E2) were decreased in F0 adults exposed to LC5 and LC10. Interestingly, in the F1 generation, total duration of Np was significantly decreased while total duration of E2 was increased in LC5 treatment. Taken together, our results showed that an LC5 of thiamethoxam induces intergenerational hormetic effects on the demographic parameters and feeding behavior of F1 individuals of S. graminum. These findings have important implications on chemical control against S. graminum and highlight the need for a deeper understanding of the ecological consequences of such exposures within pest management strategies across the agricultural landscapes.

3D-QSAR pharmacophore modeling, virtual screening, molecular docking, MD simulations, in vitro and in vivo studies to identify potential anti-hyperplasia drugs.

Psoriasis is a common immune-mediated skin condition characterized by aberrant keratinocytes and cell proliferation. The purpose of this study was to explore the FDA-approved drugs by 3D-QSAR pharmacophore model and evaluate their efficiency by in-silico, in vitro, and in vivo psoriasis animal model. A 3D-QSAR pharmacophore model was developed by utilizing HypoGen algorithm using the structural features of 48 diaryl derivatives with diverse molecular patterns. The model was validated by a test set of 27 compounds, by cost analysis method, and Fischer's randomization test. The correlation coefficient of the best model (Hypo2) was 0.9601 for the training set while it was 0.805 for the test set. The selected model was taken as a 3D query for the virtual screening of over 3000 FDA-approved drugs. Compounds mapped with the pharmacophore model were further screened through molecular docking. The hits that showed the best docking results were screened through in silico skin toxicity approach. Top five hits were selected for the MD simulation studies. Based on MD simulations results, the best two hit molecules, that is, ebastine (Ebs) and mebeverine (Mbv) were selected for in vitro and in vivo antioxidant studies performed in mice. TNF-α and COX pro-inflammatory mediators, biochemical assays, histopathological analyses, and immunohistochemistry observations confirmed the anti-inflammatory response of the selected drugs. Based on these findings, it appeared that Ebs can effectively treat psoriasis-like skin lesions and down-regulate inflammatory responses which was consistent with docking predictions and could potentially be employed for further research on inflammation-related skin illnesses such as psoriasis.

Rocephin-graphene oxide-silver nanocomposites: A versatile platform for biomedical applications.

For many years, the synthesis of graphene oxide (GO) had involved exfoliating graphite flakes, and the methods applied were expensive and time-consuming. Thus, an attempt had been made to create an inventive, less expensive method for the synthesis of GO using unrefined, raw carbon-containing material. Modified Hummer's method was used to prepare GO from banana peel. In addition, the metallic silver nanocomposite was also synthesized along with laoding of drug Rocephin where they interact with each other through electrostatic hydrogen bond interaction. The degree of crystallinity and the crystallite size were through x-ray diffraction (XRD) analysis and the crystallite size of AgNPs was found to be 40.40 nm. The scanning electron microscopy (SEM) analysis shows that the morphology of the GO gradually changes with the addition of AgNPs and Rocephin. A blue shift was seen in the absorbance maxima of the raw carbon upon the conjugation of Rocephin in UV analysis. The Fourier-transform infrared spectroscopy, and energy dispersive X-ray (EDX) spectroscopy were used to determine the chemical composition of the samples. Furthermore, a broad biological screening of the synthesized samples had been carried out following the total reducing power (TRP), total antioxidant capacity (TAC), antibacterial, antifungal, MTT (Cytotoxicity of biologically synthesized silver nanoparticles in MDA-MB-231 human breast cancer cells) cell viability, brine shrimp lethality, and hemolytic protocols. Significant results were obtained, and the Rocephin-GO-AgNPs had depicted promising activity as compared with their counterparts. RESEARCH HIGHLIGHTS: The GO was prepared from the raw carbon extracted from banana peels and was used as a substrate for the synthesis Graphene oxide silver nanoparticles (GO-AgNPs) and Rocephin-loaded graphene oxide silver nanoparticles (Rocephin-GO-AgNPs) The structural and compositional analysis of the nanomaterial was carried out, and they were screened for several biomedical applications. The Rocephin-GO-AgNPs exhibit the highest activity as compared with their counterparts.

Polyphenolic characterization and biological assessment of Acacia nilotica (L.) wild. Ex delilie: An In vitro and In vivo appraisal of wound healing potential.

ETHNOPHARMACOLOGICAL RELEVANCE: Acacia nilotica (L.) Wild. Ex Delilie is a shrub with significant ethnomedicinal stature. Therefore, in the undertaken study, its wound healing attributes are determined. AIM OF THE STUDY: The current study provided evidence of the traditional use of A. nilotica species and conferred A. nilotica bark extract as a potent candidate for wound healing agents. MATERIALS & METHODS: A. nilotica leaves extract (ANL-E); A. nilotica bark extract (ANB-E), and A. nilotica stem extract (ANS-E) were prepared using methanol-chloroform (1:1). Phytochemical analysis was performed using gallic acid equivalent (GAE) total phenolic content (TPC), quercetin equivalent (QE) total flavonoid content (TFC) assays and High-performance liquid chromatography (HPLC). In vitro antioxidant potential (free radical scavenging activity (FRSA), total antioxidant capacity (TAC), and ferric reducing antioxidant power (FRAP) assay), antibacterial activity (broth microdilution method) and hemolytic analysis was carried out. Wound healing proficiency of ANB-E was determined by wound excision model followed by estimating hydroxyproline content and endogenous antioxidant markers. RESULTS: Maximum phenolic and flavonoid content were depicted by ANB-E i.e., 50.9 ± 0.34 µg gallic acid equivalent/mg extract and 28.7 ± 0.13 µg quercetin equivalent/mg extract, respectively. HPLC analysis unraveled the presence of a significant amount of catechin in ANL-E, ANB-E and ANS-E (54.66 ± 0.02, 44.9 ± 0.004 and 31.36 ± 0.02 µg/mg extract) respectively. Highest percent free radical scavenging activity, total antioxidant capacity, and ferric reducing action power (i.e., 93.3 ± 0.42 %, 222.10 ± 0.76, and 222.86 ± 0.54 µg ascorbic acid equivalent/mg extract) were exhibited by ANB-E. Maximum antibacterial potential against Staphylococcus aureus was exhibited by ANB-E (MIC 12.5 µg/ml). Two of the extracts i.e., ANL-E and ANB-E were found biocompatible with less than 5 % hemolytic potential. Based upon findings of in vitro analysis, ANB-E (10, 5, and 2.5 % w/w, C1, C2, and C3, respectively) was selected for evaluating its in vivo wound healing potential. Maximum contraction of wound area and fastest epithelization i.e., 98 ± 0.05 % and 11.2 ± 1.00 (day) was exhibited by C1. Maximum hydroxyproline content, glutathione, catalase, and peroxidase were demonstrated by C1 i.e., 15.9 ± 0.52 µg/mg, 9.3 ± 0.17 mmol/mg, 7.2 ± 0.17 and 6.2 ± 0.14 U/mg, respectively. Maximal curbed lipid peroxidation i.e., 0.7 ± 0.15 mmol/mg was also depicted by C1. CONCLUSIONS: In a nutshell, the current investigation endorsed the wound healing potential of ANB-E suggesting it to be an excellent candidate for future studies.

Mycotoxin detection in selected medicinal plants using chromatographic techniques.

Mycotoxins are toxic mycological products that when consumed, absorbed or inhaled cause sickness or even the death of humans. Therefore, the present study aimed to evaluate the contamination levels of mycotoxins (aflatoxins, AFB1 , AFB2 , AFG1 , AFG2 , and ochratoxin A, OTA) in selected medicinal herbs and shrubs using thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). A total of 15 samples of medicinal herbs and shrubs were selected. Among them, four samples were aflatoxin contaminated while two samples were ochratoxin A contaminated. The highest level of aflatoxin was detected in Justicia adhathoda (4,704.94 ppb) through HPLC (153.4 ppb) and through TLC, while the lowest level of aflatoxin was detected in Pegnum harmala (205.1 ppb) through HPLC. Similarly, the highest level of OTA was detected in Dodonia viscosa (0.53 ppb) through HPLC (0.5 ppb) and through TLC, while the lowest level was detected in J. adhathoda (O.11 ppb) through HPLC (0.4 ppb) and through TLC. The OTA concentration was very low, being negligible and below permissible limits. The present study concludes that there is a potential risk for the consumption of herbal decoctions. Therefore, regular monitoring and proper management of mycotoxins, including aflatoxins and OTA, in herbal medicines are needed to ensure the safety of herbal drugs to protect consumers.

Mechanistic insight into the synergistic antimicrobial potential of Fagonia indica Burm.f. extracts with cefixime.

Fagonia indica Burm.f. is known for its anti-infective character and has been studied in the present work as a synergistic remedy against resistant bacterial strains. Initially, phytochemicals were quantified in n-Hexane (n-Hex), ethyl acetate (E.A), methanol (MeOH), and aqueous (Aq.) extracts by Total Phenolic Content (TPC), Total Flavonoid Content (TFC) and Reverse Phase High Performance Liquid Chromatography (RP-HPLC) analysis. Later, after establishing an antibacterial resistance profile for extracts and antibiotics against gram-positive and gram-negative strains, synergism was evaluated in combination with cefixime through time-kill kinetics and bacterial protein estimation studies. Topographic images depicting synergism were obtained by scanning electron microscopy for Methicilin-resistant Staphylococcus aureus (MRSA) and Resistant Escherichia coli (R.E. coli). Results showed the presence of maximum phenolic (28.4 ± 0.67 µg GAE/mg extract) and flavonoid (11 ± 0.42 µg QE/mg extract) contents in MeOH extract. RP-HPLC results also displayed maximum polyphenols in MeOH extract followed by E.A extract. Clinical strains were resistant to cefixime whereas these were moderately inhibited by all extracts (MIC 150-300 µg/ml) except Aq. extract. E.A and n-Hex extracts demonstrated maximum synergism (Fractional inhibitory concentration index (FICI) 0.31) against R.E. coli. The n-Hex extract displayed total synergism against R.P. a with a 4-fold reduction in cefixime dose. Time-kill kinetics showed maximum inhibition of gram-negative bacterial growth from 3 to 12 h when treated at FICI and 2FICI values with > 10-fold reduction of the extracts' dose. All combinations demonstrate > 70 % protein content inhibition with bacterial cell wall disruption in SEM images. Fortunately, FICI concentrations have low hemolytic potential (<5%). Conclusively, F. indica extracts can mitigate antimicrobial resistance against cefixime and can be investigated in detail by in vivo and mechanistic studies.

Methyl eugenol aromatherapy: a delivery system facilitating the simultaneous application of male annihilation and sterile insect technique against the peach fruit fly.

BACKGROUND: The peach fruit fly, Bactrocera zonata (Saunders) (Diptera: Tephritidae) is an economically important polyphagous, quarantine pest endemic to South and South-East Asia. The male annihilation technique (MAT) and the sterile insect technique (SIT) are environmentally benign techniques used to suppress fruit fly populations on an area-wide basis. The MAT and SIT are typically used sequentially to avoid killing released sterile males; however, MAT and SIT potentially could be used simultaneously and thereby increase the overall efficiency of control programmes. Mating competitiveness of sterile males against wild counterparts is critical for the success of the SIT. Feeding on a semiochemical, methyl eugenol (ME) has been reported to enhance the male mating performance of many Bactrocera spp., including B. zonata, but its use in SIT operational programmes is limited owing to the absence of a viable delivery system. RESULTS: In the present study, we demonstrated that ME aromatherapy, a practical method for large-scale delivery of ME olfactorily, enhances the mating success of treated B. zonata males. ME aromatherapy application to 5-day-old immature males for a duration of 5 h resulted in increased mating success of males tested when sexually mature, compared to untreated males. The ME-aromatized males also exhibited reduced attraction to ME-lure. CONCLUSION: A practical delivery system for applying ME by aromatherapy to mass-reared males was developed. ME-aromatherapy enhanced male mating success and suppressed their subsequent attraction to ME, thus enabling the application of MAT and SIT at the same time. © 2023 Society of Chemical Industry.

In vitro and in vivo antioxidant therapeutic evaluation of phytochemicals from different parts of Dodonaea viscosa Jacq.

Introduction: Natural antioxidants are vital to promote health and treat critical disease conditions in the modern healthcare system. This work adds to the index of natural medicines by exploring the antioxidant potential of Dodonaea viscosa Jacq. (Plant-DV). Material and Methods: The aqueous extract of leaves and flower-containing seeds from plant-DV in freshly prepared phosphate buffer is evaluated for antioxidant potential. In vitro antioxidant potential of the nascent and oxidatively stressed extracts was analyzed through glutathione (GSH) assay, hydrogen peroxide (H2O2) scavenging effect, glutathione-S-transferase (GST) assay, and catalase (CAT) activity. In vivo therapeutic assessment is performed in Wistar Albino rats using vitamin C as a positive control. The livers and kidneys of individual animals are probed for glutathione, glutathione-S-transferase, and catalase activities. Results: flower-containing seeds have GSH contents (59.61 µM) and leaves (32.87 µM) in the fresh aqueous extracts. The hydrogen peroxide scavenging effect of leaves is superior to flower-containing seeds with 17.25% and 14.18% respectively after 30 min incubation. However, oxidatively stressed extracts with Ag(I) and Hg(II) show declining GSH and GST levels. The plant extracts are non-toxic in rats at 5000 mg/Kg body weight. Liver and kidneys homogenate reveal an increase in GSH, GST, and CAT levels after treatment with 150 ± 2 mg/kg and 300 ± 2 mg/kg body weight plant extract compared with normal saline-treated negative and vitamin C treated positive control. Discussion: The crude aqueous extracts of leaves and flower-containing seeds of plant-DV show promising antioxidant potential both in in vitro and in vivo evaluation.

Bioassays guided isolation of berberine from Berberis lycium and its neuroprotective role in aluminium chloride induced rat model of Alzheimer's disease combined with insilico molecular docking.

OBJECTIVE: Berberis lycium is an indigenous plant of Pakistan that is known for its medicinal properties. In the current study, we investigated the anti-Alzheimer's effect of berberine isolated from Berberis lycium. METHODS: Root extract of B. lycium was subjected to acetylcholinesterase inhibition assay and column chromatography for bioassays guided isolation of a compound. The neuroprotective and memory improving effects of isolated compound were evaluated by aluminium chloride induced Alzheimer's disease rat model, elevated plus maze (EPM) and Morris water maze (MWM) tests., Levels of dopamine and serotonin in rats brains were determined using HPLC. Moreover, western blot and docking were performed to determine interaction between berberine and ß-secretase. RESULTS: During fractionation, ethyl acetate and methanol (3:7) fraction was collected from solvent mixture of ethyl acetate and methanol. This fraction showed the highest anti-acetylcholinesterase activity and was alkaloid positive. The results of TLC and HPLC analysis indicated the presence of the isolated compound as berberine. Additionally, the confirmation of isolated compound as berberine was carried out using FTIR and NMR analysis. In vivo EPM and MWM tests showed improved memory patterns after berberine treatment in Alzheimer's disease model. The levels of dopamine, serotonin and activity of antioxidant enzymes were significantly (p<0.05) enhanced in brain tissue homogenates of berberine treated group. This was supported by decreased expression of ß-secretase in berberine treated rat brain homogenates and good binding affinity of berberine with ß-secretase in docking studies. Binding energies for interaction of ß-secretase with berberine and drug Rivastigmine is -7.0 kcal/mol and -5.8 kcal/mol respectively representing the strong interactions. The results of docked complex of secretase with berberine and Rivastigmine was carried out using Gromacs which showed significant stability of complex in terms of RMSD and radius of gyration. Overall, the study presents berberine as a potential drug against Alzheimer's disease by providing evidence of its effects in improving memory, neurotransmitter levels and reducing ß-secretase expression in the Alzheimer's disease model.

Epithelioid hepatic angiomyolipoma in pregnancy: A case report.

INTRODUCTION AND IMPORTANCE: Epithelioid hepatic angiomyolipoma (HAML) is a rare benign tumor predominantly found in women. Its occurrence during pregnancy is extremely rare. Accurate diagnosis of HAML is challenging due to its radiological resemblance to other hepatic neoplasms. We present a case of epithelioid HAML in a pregnant patient, highlighting the diagnostic and management challenges encountered. CASE PRESENTATION: A 24-year-old pregnant female, in her fifth month of pregnancy, presented with right hypochondrium pain and nausea. Radiological imaging suggested the possibility of a hepatic adenoma. The patient opted to continue the pregnancy with regular monitoring of the mass as well as fetal health. After delivering a healthy baby, the patient underwent successful mass excision and cholecystectomy. Histopathology of the liver mass confirmed the diagnosis of epithelioid HAML. CLINICAL DISCUSSION: Epithelioid HAML is a rare tumor often misdiagnosed. It is more aggressive and frequently associated with tuberous sclerosis complex (TSC) compared to other subtypes. The diagnosis of HAML can be challenging due to its resemblance to Hepatocellular Carcinoma and other hepatic neoplasms on radiological imaging. Immunohistochemistry plays a crucial role in confirming the diagnosis. Surgical excision is the recommended treatment, with complete removal to minimize the risk of recurrence. CONCLUSION: This case report highlights the rarity of epithelioid HAML during pregnancy and emphasizes the importance of a multidisciplinary approach in managing hepatic neoplasms. Close monitoring is crucial, considering the potential risks to the mother and fetus. Accurate diagnosis through histopathological evaluation, immunohistochemistry and a multidisciplinary approach are essential for appropriate management.

Artemisia brevifolia Wall. Ex DC Enhances Cefixime Susceptibility by Reforming Antimicrobial Resistance.

(1) Background: A possible solution to antimicrobial resistance (AMR) is synergism with plants like Artemisia brevifolia Wall. ex DC. (2) Methods: Phytochemical quantification of extracts (n-hexane (NH), ethyl acetate (EA), methanol (M), and aqueous (Aq)) was performed using RP-HPLC and chromogenic assays. Extracts were screened against resistant clinical isolates via disc diffusion, broth dilution, the checkerboard method, time-kill, and protein quantification assays. (3) Results: M extract had the maximum phenolic (15.98 ± 0.1 µg GAE/mgE) and flavonoid contents (9.93 ± 0.5 µg QE/mgE). RP-HPLC displayed the maximum polyphenols in the M extract. Secondary metabolite determination showed M extract to have the highest glycosides, alkaloids, and tannins. Preliminary resistance profiling indicated that selected isolates were resistant to cefixime (MIC 20-40 µg/mL). Extracts showed moderate antibacterial activity (MIC 60-100 µg/mL). The checkerboard method revealed a total synergy between EA extract and cefixime with 10-fold reductions in cefixime dose against resistant P. aeruginosa and MRSA. Moreover, A. brevifolia extracts potentiated the antibacterial effect of cefixime after 6 and 9 h. The synergistic combination was non- to slightly hemolytic and could inhibit bacterial protein in addition to cefixime disrupting the cell wall, thus making it difficult for bacteria to survive. (4) Conclusion: A. brevifolia in combination with cefixime has the potential to inhibit AMR.

Laboratory-Induced Bifenthrin, Flonicamid, and Thiamethoxam Resistance and Fitness Costs in Rhopalosiphum padi.

The bird cherry-oat aphid, Rhopalosiphum padi (L.) (Hemiptera: Aphididae) is one of the most economically important pests of wheat crops worldwide. Thiamethoxam, bifenthrin, and flonicamid are extensively used insecticides for controlling this key pest. However, the indiscriminate use of chemical insecticides has led to the development of resistance in insects. In this study, we assessed the development of selection-induced resistance to bifenthrin, flonicamid, and thiamethoxam under controlled laboratory conditions. Additionally, we employed the age-stage, two-sex life table method to examine the fitness of R. padi. After ten generations of selection, bifenthrin-, flonicamid-, and thiamethoxam-resistant strains of R. padi were developed with resistance levels of 34.46, 31.97, and 26.46-fold, respectively. The life table analysis revealed a significant decrease in adult longevity and fecundity in these resistant strains compared to susceptible strain. Furthermore, the key demographic parameters such as net reproductive rate (R0) and reproductive days exhibited a significant reduction in all resistant strains, while the intrinsic rate of increase (r) and finite rate of increase (λ) were decreased only in resistant strains to bifenthrin and thiamethoxam. Taken together, these findings provide a comprehensive understanding of laboratory-induced insecticide resistance evolution and the associated fitness costs in R. padi. This knowledge could help to design resistance management strategies against this particular pest of wheat.

Donor Safety First: Postoperative Hepatectomy Outcomes in Living Liver Donors.

BACKGROUND: Living donor liver transplantation (LDLT) has become a popular treatment option because some countries lack a deceased organ program and the growing demand for liver transplants. Although postoperative outcomes are similar to deceased donor liver transplants, there is still an element of risk to the donor. The Clavien-Dindo classification system has been used to standardize reporting across different institutions and surgeons to categorize surgical outcomes. METHODS: Between January 1, 2022, and December 31, 2022, 207 living donors underwent hepatectomies at our center. All donors underwent a 3-step process of mandatory screening. Postsurgical complications were classified using the Clavien-Dindo classification. RESULTS: A total of 207 donor hepatectomies for LDLT were performed during our study period. Most donors (92.8%) were aged between 18 and 39 years. The most common type of graft used was a right lobe without the middle hepatic vein (82.6%). Most donors (91.7%) experienced an intraoperative blood loss of ≤500 mL. A total of 140 patients had an ordinary postoperative course. Grade 1 complications were observed in 16.9%, grade 2 in 12.1%, and grade 3 in 3.4% of the remaining patients. No grade 4 or grade 5 (patient death) complications were observed in this cohort. CONCLUSIONS: Living donor liver transplantation remains the most practiced liver transplant surgery in Pakistan. Our findings highlight the safety of the LDLT program with minimal risk of significant complications. The study also underscores the importance of careful screening and monitoring of living donors and the need for standardized reporting of surgical outcomes using the Clavien-Dindo classification system.

Green synthesis of cobalt ferrite and Mn doped cobalt ferrite nanoparticles: Anticancer, antidiabetic and antibacterial studies.

BACKGROUND: CoFe2O4 are important magnetic NPs with high coercivity and moderate magnetization. These properties of CoFe2O4 NPs show variation when doped with various metals. Recent studies explained that Cobalt ferrites doped with metal ion like Mn+2, have attracted increasing attention in many applications, particularly in biomedical applications. A relatively simple way is employing plants and their extracts as precursors instead of toxic chemicals to produce NPs with desirable characteristic. In current study we report green synthesis and characterization of magnetic (CoFe2O4, MnCoFe2O4, CoFe2O4@S.C, MnCoFe2O4@S.C) nanoparticles using ethanolic extract of Swertia Chirata. To enhance application as biocompatible magnetic nano drug delivery vector and cell targeting efficacy of drugs, Glimepiride (GLM), Dexamethasone (DXM), Fexofenadine (FEX) and Levofloxacin (LVX) 1were loaded on synthesized NPs. Synthesized CFNPs has been broadly characterized and applied for in vitro anticancer, antidiabetic and antibacterial potential. METHODS: For synthesis of CoFe2O4 (CF), CoMnFe2O4 (CFM), CoFe2O4@S.C (SCF) & CoMnFe2O4 @S.C (SCFM), stochiometric amounts 5 mmol of CoCl2·6 H2O (0.284 g) and 10 mmol FeCl3·6 H2O (0.378 g) were dissolved in 13 mL of deionized water. To this sodium acetate (3.05 g) and urea (0.6 g) were added until complete dissolution. Afterward n-heptane was added, and contents were then transferred to Teflon lining autoclave at 180 °C for 4 h. Black powder CoFe2O4 NPs after washing, were dried and calcined at 450 oC for 2 h. RESULTS: XRD diffractogram of CF have proved the single-phase cubic spinel structure formation for all samples. Swertia Chirata formulations were shown to have effective in vitro antidiabetic activity. CF, CFM & SCFM showed good inhibition of α-glucosidase with very low concentration 6 µg/mL, 5 µg/mL and 4 µg/mL as compare to 12.41 µg/mL of acarbose. SCF showed that the value slightly higher than 16 µg/mL compared to standard. Drug loaded CFNPs (L-CFNPs, F-CFNPs, D-CFNPs & G-CFNPs) also effectively inhibited α-glucosidase. IC50 value for CFNPs inhibition of α-glucosidase was 12.4 µg/mL. All synthesized CF NPs showed cytotoxic potential against breast cancer cells MCF-7. About 50-60% cell viability and cytotoxicity 40% were observed for bare CFNPs as compare to Doxorubicin with related toxicity 80% and 20% cell viability. Among synthesized samples almost all samples without conjugation of any drug showed activities against at least one bacterial strain. CFM, SCF, SCFM were active against S. aureus at concentration 100 µg/mL, 100 µg/mL, and 50 µg/mL respectively. CONCLUSION: The synthesized CF NPs showed significant cytotoxic potential against MCF-7 breast cancer cell line. Further, drug loaded samples displayed lesser cell viability and slightly increased cytotoxicity in range of 40-50% in comparison with bare CFNPs. However, higher toxicity was observed for CFMGS towards MCF-7 cells with results nearly equal to Doxorubicin with significant decrease in viability. CF, CFM & SCFM showed good inhibition of α-glucosidase with very low concentration 6 µg/mL, 5 µg/mL and 4 µg/mL as compare to 12.41 µg/mL of acarbose. Among synthesized samples almost all samples without conjugation of any drug showed activities against at least one bacterial strain.

Impact of sublethal concentrations of flonicamid on key demographic parameters and feeding behavior of Schizaphis graminum.

Flonicamid is a novel systemic insecticide that efficiently controls sap-sucking insect pests. However, the impact of sublethal concentrations of flonicamid on key demographic parameters and the feeding behavior of greenbug, Schizaphis graminum has not yet been studied. In this study, we used the age stage, two-sex life table approach, and electrical penetration graphs (EPGs) to investigate the sublethal effects of flonicamid on the biological traits and feeding behavior of S. graminum. Bioassays showed that flonicamid possesses high toxicity to adult S. graminum with LC50 of 5.111 mg L-1 following 48 h exposure. Sublethal concentrations of flonicamid (LC5 and LC10) significantly decreased the longevity and fecundity of directly exposed parental aphids (F0), while the reproductive days were reduced only at LC10. The pre-adult stage and total pre-reproductive period (TPRP) increased in F1 individuals after exposure of F0 aphids to the sublethal concentrations of flonicamid. Furthermore, the adult longevity, fecundity and key demographic parameters (R0, r, and λ) were significantly reduced in progeny generation (F1). EPG recordings showed that the total duration of phloem sap ingestion and concurrent salivation (E2) decreased substantially in F0 and F1 aphids after exposure to LC5 and LC10 of flonicamid. Taken together, our results showed that the sublethal concentrations of flonicamid affect the demographic parameters and feeding behavior that ultimately suppress the population growth of S. graminum. This study provides in-depth information about the overall effects of flonicamid on S. graminum that might help to manage this key pest.

Development and validation of HPLC method for simultaneous determination of Leflunomide and folic acid in the nanoparticulate system by reversed-phase HPLC.

OBJECTIVE: The main objective of this study was to develop a highly sensitive, accurate, and reproducible analytical method for the simultaneous detection of LEF and FA in polymeric nanocarriers. SIGNIFICANCE: Leflunomide (LEF), is widely employed in the treatment of rheumatoid arthritis (RA). However, long-term delivery of the drug is associated with systemic side effects. Therefore, folate (FA) conjugated LEF nanocarriers were fabricated for targeting the nanocarriers toward activated macrophages. HPLC is considered one of the most sensitive and precise analytical techniques for the simultaneous detection and estimation of different components in a particular sample. METHODS: Analysis was performed on HPLC (Shimadzu 10 A), having a reversed-phase C-18 column (Beckmen, 250 X 4.6 mm, 5 µm) equipped with a photodiode detector set at a wavelength of 260 nm (LEF) and 285 nm (Folic acid). The isocratic mobile phase was composed of acetonitrile, water, and trimethylamine in a ratio of 65:35:0.5 at pH 4. Rapid analysis of both agents was performed, with a total run time of 10 min (FA = 2.1 ± 0.1 min, LEF = 5.9 ± 1 min) at a 1 mL/min flow rate. RESULTS: The assay demonstrated good linearity of 0.9989 of 0.9997 for LEF and FA respectively with a recovery in the range of 95-100%. The method also depicted good specificity, and intra and inter-day precision based on relative standard deviation (RSD) values. CONCLUSIONS: The study concludes, that the developed method was helpful in the detection and quantitation of lower values of both agents from polymeric nanocarriers.

HighlightsOptimization and validation of the RP-HPLC method were performed for the simultaneous detection of LEF and FA.Validation was performed on the basis of linearity, accuracy, precision, LOD, LOQ, and robustness in accordance with ICH criteria.Validated analytical procedure was employed for the simultaneous detection of LEF and FA from polymeric nanocarriers.The proposed analytical method is reliable, fast, robust, and can be successfully applied for quantification of % EE, and % DL in polymeric nanocarriers.

Thymus linearis Extracts Ameliorate Indices of Metabolic Syndrome in Sprague Dawley Rats.

Materials and Methods: The extract library (n-hexane (NH), ethyl acetate (EA), methanol (M), distilled water (DW), and combined extract (CE)) was standardized using in vitro phytochemical, antioxidant, and α-amylase inhibition assays, after which the protective effect of selected "hit," i.e., CE against metabolic syndrome, was determined in vivo, using rats fed a high-fat diet supplemented with additional cholesterol administration. CE was administered to Sprague Dawley rats in high dose as 100 mg/kg in carboxymethyl cellulose (CMC) (1 ml; 0.75% in DW) and low-dose group as 50 mg/kg in CMC (0.5 ml; 0.75% in DW). After 10 weeks, the effects of CE on insulin resistance, lipid metabolism, nonalcoholic fatty liver disease (NAFLD), oxidative stress, and genotoxicity were assessed through histological, biochemical, and hematological investigations. Results: Phytochemical analysis including RP-HPLC analysis of the extracts showed that flavonoids and phenolics (myricetin, kaempferol, and apigenin), previously known to be effective against obesity and diabetes, are present in the extracts. Antioxidant studies revealed that the plant possesses a highly significant (p < 0.05) concentration of antioxidants. Satisfactory α-amylase inhibitory activity was also observed in in vitro experiments. In vivo studies showed that CE-administered animals had significantly (p < 0.05) lower weight gain and smaller adipocytes than the control group. Moreover, CE resisted any significant (p < 0.05) change in the organ weights. Analogous to findings from its traditional use, the plant extract had a positive modulatory effect on insulin resistance and hyperglycemia. The study also indicated that CE resisted high-fat diet-induced disturbance in lipid profile and countered any pathological changes in liver enzymes caused by fat-infused diet. Furthermore, a study on endogenous antioxidant levels indicated that CE was effective in maintaining catalase and peroxidase levels within the normal range and resisted the effects of lipid peroxidation of thiobarbituric acid reactive substances. Conclusion: In principle, the current study's findings scientifically validate the implication of T. linearis in metabolic syndrome and recommend further studies on molecular insights of the observed therapeutic activity.

Liver Transplantation: A Right or a Privilege? Sustainable Liver Transplant Financing With an Innovative Model for the Developing World.

Living donor liver transplant in addition to its lifesaving therapy is a cost-effective alternate to long-term disease management in patients with chronic liver disease. Financial constraint is the biggest hurdle faced by patients in developing countries in availing the liver transplantation. So, we conducted this study to report a government-funded financial support system for liver transplant services. A total of 198 patients who underwent living donor liver transplant with at least 90 days follow-up were included in the study. According to proxy means test score, 52.2% patients were from low and middle socioeconomic groups and 64.6% of patients underwent liver transplantation through government support. Out of 198 patients who underwent liver transplantation 29.6% had monthly income below 25,000 Pakistani rupees ($114). In recipients, 90-day mortality was 7.1% and morbidity was 67.1%. Donor morbidity was 23.2% without any mortality. This financial model can serve as a valuable source for middle and low income group countries to overcome the financial challenge and make liver transplant an accessible, affordable, and economically viable option.