Nucleoredoxin 1 positively regulates heat stress tolerance by enhancing the transcription of antioxidants and heat-shock proteins in tomato.

Thioredoxins (TRXs) are small oxidoreductase proteins located in various subcellular compartments. Nucleoredoxin (NRX) is a nuclear-localized TRX and a key component for the integration of the antioxidant system with the immune response. Although NRX is well characterized in biotic stress responses, its functional role in abiotic stress responses is still elusive. To understand whether NRX contributes to heat stress response in tomato (Solanum lycopersicum), we generated CRISPR/Cas9-mediated mutations in SlNRX1 (slnrx1). Interestingly, the slnrx1 mutant was extremely sensitive to heat stress with higher electrolyte leakage, malondialdehyde contents, and H2O2 concentration compared to wild-type tomato plants, suggesting that SlNRX1 negatively regulates heat stress-induced oxidative damage. We also found that transcripts encoding antioxidant enzymes and Heat-Shock Proteins (HSPs) in slnrx1 were down-regulated either in the absence or presence of heat stress. These data suggest that NRX1 is a positive regulator for heat stress tolerance by elevating antioxidant capacity and inducing HSPs to protect cells against heat stress-induced oxidative damage and protein denaturation, respectively.

Synthesis and Characterization of Novel Hydrazone Derivatives of Isonicotinic Hydrazide and Their Evaluation for Antibacterial and Cytotoxic Potential.

Hydrazones are active compounds having an azomethine -NHN=CH group and are widely studied owing to their ease of preparation and diverse pharmacological benefits. Novel isonicotinic hydrazone derivatives of vanillin aldehyde and salicyl aldehyde were synthesized that had azomethine linkages and were characterized by UV-Visible, FTIR, EI-MS, 1H-NMR and 13C-NMR spectroscopy. The compounds were screened for their antibacterial activity against Staphylococcus aureus, Bacillus subtilus, and Escherichia coli using disc diffusion and minimum inhibitory concentration (MIC) methods. For cytotoxicity, a brine shrimp lethality test was performed to calculate the lethal concentration (LC50). The results demonstrated appreciable antibacterial activities against the applied strains, amongst which the compounds coded NH3 and NH5 showed maximum inhibition and MIC responses. In terms of cytotoxic activity, the maximum effect was observed in compound NH5 and NH6 treatments with minimum survival percentages of 36.10 ± 3.45 and 32.44 ± 2.0, respectively. These hydrazones could be potential candidates in antitumorigenic therapy against various human cancer cells.

A Significant Change in Free Amino Acids of Soybean (Glycine max L. Merr) through Ethylene Application.

In this study, the changes in free amino acids of soybean leaves after ethylene application were characterized based on quantitative and metabolomic analyses. All essential and nonessential amino acids in soybean leaves were enhanced by fivefold (250 to 1284 mg/100 g) and sixfold (544 to 3478 mg/100 g), respectively, via ethylene application. In particular, it was found that asparagine is the main component, comprising approximately 41% of the total amino acids with a twenty-five fold increase (78 to 1971 mg/100 g). Moreover, arginine and branched chain amino acids (Val, Leu, and Ile) increased by about 14 and 2-5 times, respectively. The increase in free amino acid in stem was also similar to the leaves. The metabolites in treated and untreated soybean leaves were systematically identified by gas chromatography-mass spectrometry (GC-MS), and partial variance discriminant analysis (PLS-DA) scores and heat map analysis were given to understand the changes of each metabolite. The application of ethylene may provide good nutrient potential for soybean leaves.

Synthesis and characterization of pyridine-based organic salts: Their antibacterial, antibiofilm and wound healing activities.

In treating wounds, long lasting infection is considered the major impediment. Drugs are rendered ineffective by pathogenic microorganisms via antibiotic resistance and calls for designing and development of new drugs. Herein, we report synthesis of eight different N-alkylated pyridine-based organic salts QAS 1-8 and their antibacterial, antibiofilm and wound healing activities. 3-(2-R-hydrazinecarbonyl)-1-propylpyridinium Bromide was the parent compound while R group was varying in each salt composed of different aromatic aldehyde moieties. In the antibacterial activity against S. aureus and E. coli, amoxicillin shows IC50 near to 25 µg/mL inhibiting 58 ± 0.4% S. aureus while ceftriaxone inhibited 55 ± 0.5% E. coli at a concentration of 10 µg/mL. The highest IC50 (56 ± 0.5% against S. aureus; 55 ± 0.5% against E. coli) was shown by compound QAS 7 at the concentration of 100 µg/mL; followed by the QAS 6 (55 ± 0.5% against E. coli) and QAS 2 (55 ± 0.5% against E. coli). In the antibiofilm activity, QAS 6, QAS 1 and QAS 8 inhibited 58 ± 0.4% S. aureus at a concentration of 75 µg/mL, while QAS 2 inhibited E. coli at the same concentration and amount. QAS 7, 3 and 1 inhibited almost 90% while QAS 6 inhibited 95 ± 1.1%of E. coli at a concentration of 250 µg/mL. Highest MBIC was provided by QAS 7 (52 ± 0.4%) against S. aureus at a concentration of 50 µg/mL that is very near to the standard amoxicillin. Antibacterial and antibiofilm activity results were also supported by the atomic force microscopy (AFM). In the wound healing activity, QAS 8 healed 90.8 ± 4.3% of the wound in 21 days with an average period of epithelialization (POE) of 19 ± 1.4 days; that is far better than povidone iodine ointment (81.5 ± 3.3% of the wound in the 21 days with 22.4 ± 2.9 days of POE). It is concluded from this study that the synthesized compounds QAS 2, 7 and 8 can be used for further mechanistic studies to be employed as antibacterial, antibiofilm and wound healing agents.

Synthesis of long-tail nonionic surfactants and their investigation for vesicle formation, drug entrapment, and biocompatibility.

Nonionic surfactants have an extraordinary fascination for the researchers in the field of drug delivery for enhancing drug bioavailability and therapeutic efficacy. Here, we are reporting the synthesis, characterization, drug entrapment efficiency (EE), critical micellar concentration, and biocompatibility evaluation of sulphanilamide based new nonionic surfactants. The surfactants were synthesized in single step reactions and characterized through 1H NMR, FT-IR, and mass spectrometric analysis. The surfactants abilities for niosomal vesicles formation were investigated utilizing Ciprofloxacin as a model drug. The drug loaded niosomal suspension of the synthesized surfactants was screened for shape; size, polydispersity index, and drug EE utilizing AFM, Zetasizer, and UV, respectively. The compatibility of the drug in drug loaded vesicles with excipients was assessed utilizing FT-IR spectroscopy. The biocompatibility of the synthesized surfactants was assessed through blood haemolysis and cell cytotoxicity assays. Results of this study showed that the synthesized surfactants were quite haemocompatible and nontoxic in nature and were able to form spherical vesicles. The size and drug EE of the vesicles were dependant on the length of surfactant aliphatic chain. Surfactant with long aliphatic chain was more efficient in entrapping the drug and could be used as a potential vesicular drug delivery vehicle for improving the lipophilic drug's bioavailability.

Arabidopsis GIGANTEA negatively regulates chloroplast biogenesis and resistance to herbicide butafenacil.

KEY MESSAGE: Arabidopsis GI negatively regulates chloroplast biogenesis and resistance to the herbicide butafenacil by enhanced activity and transcriptional levels of antioxidant enzymes Chloroplast biogenesis is blocked by retrograde signaling triggered by diverse internal and external cues, including sugar, reactive oxygen species (ROS), phytohormones, and abiotic stress. Efficient chloroplast biogenesis is essential for crop productivity due to its effect on photosynthetic efficiency, and is associated with agronomic traits such as insect/disease resistance, herbicide resistance, and abiotic stress tolerance. Here, we show that the circadian clock-controlled gene GIGANTEA (GI) regulates chloroplast biogenesis in Arabidopsis thaliana. The gi-2 mutant showed reduced sensitivity to the chloroplast biogenesis inhibitor lincomycin, maintaining high levels of photosynthetic proteins. By contrast, wild-type and GI-overexpressing plants were sensitive to lincomycin, with variegated leaves and reduced photosynthetic protein levels. GI is degraded by lincomycin, suggesting that GI is genetically linked to chloroplast biogenesis. The GI mutant alleles gi-1 and gi-2 were resistant to the herbicide butafenacil, which inhibits protoporphyrinogen IX oxidase activity and triggers ROS-mediated cell death via the accumulation of chlorophyll precursors. Butafenacil-mediated accumulation of superoxide anions and H2O2 was not detected in gi-1 or gi-2, as revealed by histochemical staining. The activities of the antioxidant enzymes superoxide dismutase, peroxidase, and catalase were 1.2-1.4-fold higher in both gi mutants compared to the wild type. Finally, the expression levels of antioxidant enzyme genes were 1.5-2-fold higher in the mutants than in the wild type. These results suggest that GI negatively regulates chloroplast biogenesis and resistance to the herbicide butafenacil, providing evidence for a genetic link between GI and chloroplast biogenesis, which could facilitate the development of herbicide-resistant crops.

Creatinine-based non-phospholipid vesicular carrier for improved oral bioavailability of Azithromycin.

CONTEXT: Novel, safe, efficient and cost effective nano-carriers from renewable resources have got greater interest for enhancing solubility and bioavailability of hydrophobic dugs. OBJECTIVES: This study reports the synthesis of a novel biocompatible non-phospholipid human metabolite "Creatinine" based niosomal delivery system for Azithromycin improved oral bioavailability. METHODS: Synthesized surfactant was characterized through spectroscopic and spectrometric techniques and then the potential for niosomal vesicle formation was evaluated using Azithromycin as model drug. Drug loaded vesicles were characterized for size, polydispersity index (PDI), shape, drug encapsulation efficiency (EE), in vitro release and drug-excipient interaction using zetasizer, atomic force microscope (AFM), LC-MS/MS and FTIR. The biocompatibility of surfactant was investigated through cells cytotoxicity, blood hemolysis and acute toxicity. Azithromycin encapsulated in niosomes was investigated for in vivo bioavailability in rabbits. RESULTS: The vesicles were spherical with 247 ± 4.67 nm diameter hosting 73.29 ± 3.51% of the drug. Surfactant was nontoxic against cell cultures and caused 5.80 ± 0.51% hemolysis at 1000 µg/mL. It was also found safe in mice up to 2.5 g/kg body weight. Synthesized surfactant based niosomal vesicles revealed enhanced oral bioavailability of Azithromycin in rabbits. CONCLUSIONS: The results of the present study confirm that the novel surfactant is highly biocompatible and the niosomal vesicles can be efficiently used for improving the oral bioavailability of poor water soluble drugs.

Chemical composition, antioxidant and anticholinesterase potentials of essential oil of Rumex hastatus D. Don collected from the North West of Pakistan.

BACKGROUND: Ethnomedicinally Rumex hastatus D. Don has been used since long for various ailments especially in neurological disorders. The reported data and the importance of Rumex genus demonstrate the vital medicinal value of R. hastatus. METHODS: In the current investigational study, isolation of essential oil and its antioxidant and anticholinesterase assays were performed. The essential oil of R. hastatus was analyzed by GC-MS for the first time. The essential oil was evaluated for anticholinesterase and antioxidant assays. The anticholinesterase assay was conducted at various concentrations (62.5 to 1000 µg/ml) against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Similarly, the antioxidant potential was determined using DPPH and ABTS free radicals. RESULTS: The GC-MS analysis of essential oil showed 123 components. The result recorded for the anticholinesterase assays demonstrated a marked potential against AChE and BChE with IC50 values of 32.54 and 97.38 µg/ml respectively which were comparable with the positive control i.e., galanthamine (AChE, IC50 = 4.73 µg/ml and BChE, IC50 = 11.09 µg/ml). The antioxidant assays against DPPH and ABTS free radicals also exhibited significant scavenging potential with IC50 values of 3.71 and 6.29 µg/ml respectively, while for ascorbic acid the IC50 value was <0.1 µg/ml against both free radicals. CONCLUSIONS: Based on the current investigational studies, it may be concluded that R. hastatus is an effective source of essential oil's components having anticholinesterase and antioxidant potentials, which after subjecting to drug development may lead to novel drug candidates against neurodegenerative disorders.

Synthesis of calix (4) resorcinarene based amphiphilic macrocycle as an efficient nanocarrier for Amphotericin-B to enhance its oral bioavailability.

The supramolecular-based macrocyclic amphiphiles have fascinating attention and find extensive utilization in the pharmaceutical industry for efficient drug delivery. In this study, we designed and synthesized a new supramolecular amphiphilic macrocycle to serve as an efficient nanocarrier, achieved by treating 4-hydroxybenzaldehyde with 1-bromotetradecane. The derivatized product was subsequently treated with resorcinol to cyclize, resulting in the formation of a calix(4)-resorcinarene-based supramolecular amphiphilic macrocycle. The synthesized macrocycle and intermediate products were characterized using mass spectrometry, IR, and 1H NMR spectroscopic techniques. The amphotericin-B (Amph-B)-loaded and unloaded amphiphiles were screened for biocompatibility studies, vesicle formation, particle shape, size, surface charge, drug entrapment, in-vitro release profile, and stability through atomic force microscopy (AFM), Zetasizer, HPLC, and FT-IR. Amph-B -loaded macrocycle-based niosomal vesicles were investigated for in-vivo bioavailability in rabbits. The synthesized macrocycle exhibited no cytotoxicity against normal mouse fibroblast cells and was found to be hemocompatible and safe in mice following an acute toxicity study. The drug-loaded macrocycle-based vesicles appeared spherical, nano-sized, and homogeneous in size, with a notable negative surface charge. The vesicles remained stable after 30 days of storage. The results of Amph-B oral bioavailability and pharmacokinetics revealed that the newly tailored niosomal formulation enhanced drug solubility, protected drug degradation at gastric pH, facilitated sustained drug release at the specific target site, and delayed plasma drug clearance. Incorporating such advanced niosomal formulations in the field of drug delivery systems has the potential to revolutionize therapeutic outcomes and improve the quality of patient well-being.

Utility of the "BATS" Score in Predicting Choledocholithiasis in Patients With Gall Bladder Stones.

Background and aim The role of expensive, risky, and unnecessary endoscopic interventions can be avoided by the use of non-invasive tests to predict common bile duct (CBD) stones. Therefore, our aim was to identify non-invasive predictors of choledocholithiasis (CL) in patients and further to predict a model and assess its diagnostic accuracy in predicting CL. Methods This cross-sectional study was carried out from June 1, 2020, to December 31, 2021. Patients having gall bladder stones on percutaneous transabdominal sonography and fulfilling intermediate probability criteria of CL were enrolled. These patients then underwent radial endoscopic ultrasound (EUS) followed by endoscopic retrograde cholangiopancreatography (ERCP) for detecting CBD stones. Univariate logistic regression analysis, followed by multivariate logistic regression analysis, was performed to ascertain the independent predictors of CBD stone in patients with intermediate probability. A model was proposed, and the diagnostic accuracy was calculated at an optimal cutoff. The model was then internally validated in the patients with intermediate probability and was also compared with the pre-existing score. Results Out of 131 patients included in the study, CBD stone was noted in 85 (66%) and 88 (67.2%) patients on EUS and ERCP, respectively. On multivariate analysis, high serum bilirubin (>2 mg/dL) and alkaline phosphatase (200 IU) and dilated CBD (>6 mm) on transabdominal sonography at baseline were significant predictors of CBD stone in these patients. Using these variables, a scoring system (BATS score) was developed, which had an area under the receiver operating curve (AUROC) of 0.98 in predicting the presence of CBD stone with a sensitivity of 93.18%, a specificity of 76.74%, and a diagnostic accuracy of 87.79%. In the validation cohort, a BATS score of ≥5 had a diagnostic accuracy of 95.91% in predicting CL. Conclusion The BATS score showed excellent sensitivity and good diagnostic accuracy in predicting the CBD stone with excellent results on internal validation. However, external validation of our results is required to recommend this model on a larger scale.

Synthetic star shaped tetra-tailed biocompatible supramolecular amphiphile as an efficient nanocarrier for Amphotericin B.

Macrocycle-based amphiphiles are capable of self-assembling into multidimensional nano-architecture with defined dimensions for various applications. Herein we report the synthesis, physio-chemical characterizations and oral drug delivery profiling of resorcinarene-based amphiphilic supramolecular macrocycle. The macrocycle was synthesized in two-step reaction and characterized using 1H NMR, Mass spectrometry and IR spectroscopic techniques. The synthesized macrocycle was assessed for vesicles formation, checked for biocompatibility and then Amphotericin B (Amp-B) was entrapped in macrocycle-based vesicles. The drug loaded vesicles were characterized for shape, size, homogeneity, drug entrapment, surface charge, in-vitro release profile and stability. Amp-B loaded macrocycle based vesicles were examined in rabbits for in-vivo bioavailability and compared with plan drug suspension. The synthesized macrocycle was non-toxic in normal mouse fibroblast cells, compatible with blood and safe in mice. The drug loaded macrocycle based vesicles appeared spherical with 279.4 nm size and - 12.2 mV zeta potential loading 85.45 % drug. The drug loaded vesicles storage stability for 30 days and gastric fluid stability for 1 h were it retained nearly 90 % drug at 30th day and 83.79 % drug at 1 h in gastric fluid. Oral bioavailability of Amp-B in rabbits was markedly enhanced when delivered in synthesized macrocycle based vesicles in comparison with plan drug suspension. Results of this study indicate that the synthesized star shaped tetra-tailed supramolecular amphiphile could be used as an efficient nanocarrier for enhancing oral bioavailability of drugs with solubility and bioavailability issues like Amp-B.

Characteristics Analysis of Plasticized Polyvinyl Chloride Gel-Based Microlens at Different Temperatures.

Temperature plays a crucial role in the preparation of polyvinyl chloride (PVC) gels for optical applications. Incorrect temperature selection can lead to various issues such as poor surface roughness, inadequate light transmission, and insufficient solution for optical devices. To address this challenge, this study focuses on the preparation of PVC gel samples by combining PVC powder (n = 3000), eco-friendly dibutyl adipate, and tetrahydrofuran at different stirring temperatures ranging from 40 to 70 °C. The PVC gel preparation process is categorized into four groups (T40, T50, T60, and T70) based on the mixing temperatures, employing a controlled test method with specific temperature conditions. The prepared PVC gel samples are then subjected to analysis to evaluate various properties including surface morphology, tensile strength, light transmittance, and electrical response time. Among the samples, the PVC gel prepared at 60 °C (referred to as T60) exhibits excellent optical properties, with a transmittance of 91.2% and a tensile strength of 2.07 MPa. These results indicate that 60 °C is an optimal reaction temperature. Notably, the PVC gel microlenses produced at this temperature achieve their maximum focal length (ranging from -8 to -20 mm) within approximately 60 s, and they recover their initial state within around 80 s after the power is switched off. This focal length achievement is twice as fast as reported in previous studies on microlenses. It is observed that the reaction temperature significantly influences the solubility of the resin-based raw materials and the homogeneity of the gel. Consequently, these findings open up possibilities for utilizing PVC gel microlenses in novel commercial optics applications, thanks to their desirable properties.

Analysis of the Performance of a Gel Actuator Made of Plasticized Polyvinyl Chloride/Carboxylated Cellulose Nanocrystals.

Recently, polyvinyl chloride (PVC) gel materials appeared promising for developing actuators, artificial muscles, and sensors. However, their energized response time and recovery limitations restrict their broader applications. Herein, a novel soft composite gel was prepared by mixing functionalized carboxylated cellulose nanocrystals (CCNs) and plasticized PVC. The surface morphology of the plasticized PVC/CCNs composite gel was characterized by scanning electronic microscopy (SEM). The prepared PVC/CCNs gel composites have increased polarity and electrical actuation with a fast response time. Experimental results demonstrated good response characteristics within the actuator model with a multilayer electrode structure when stimulated with a specified DC voltage (1000 V), with deformation of approximately 36.7%. Moreover, this PVC/CCNs gel has excellent tensile elongation, and the elongation at break of the PVC/CCNs gel is greater than the elongation at break of the pure PVC gel under the same thickness conditions. However, these PVC/CCNs composite gels showed excellent properties and development potential and are directed for broad applications in actuators, soft-robotics, and biomedical applications.

Nucleoredoxin gene SINRX1 negatively regulates tomato immunity by activating SA signaling pathway.

The tomato (Solanum lycopersicum) is widely consumed globally and renowned for its health benefits, including the reduction of cardiovascular disease and prostate cancer risk. However, tomato production faces significant challenges, particularly due to various biotic stresses such as fungi, bacteria, and viruses. To address this challenges, we employed the CRISPR/Cas9 system to modify the tomato NUCLEOREDOXIN (SlNRX) genes (SlNRX1 and SlNRX2) belonging to the nucleocytoplasmic THIOREDOXIN subfamily. CRISPR/Cas9-mediated mutations in SlNRX1 (slnrx1) plants exhibited resistance against bacterial leaf pathogen Pseudomonas syringae pv. maculicola (Psm) ES4326, as well as the fungal pathogen Alternaria brassicicola. However, the slnrx2 plants did not display resistance. Notably, the slnrx1 demonstrated elevated levels of endogenous salicylic acid (SA) and reduced levels of jasmonic acid after Psm infection, in comparison to both wild-type (WT) and slnrx2 plants. Furthermore, transcriptional analysis revealed that genes involved in SA biosynthesis, such as ISOCHORISMATE SYNTHASE 1 (SlICS1) and ENHANCED DISEASE SUSCEPTIBILITY 5 (SlEDS5), were upregulated in slnrx1 compared to WT plants. In addition, a key regulator of systemic acquired resistance, PATHOGENESIS-RELATED 1 (PR1), exhibited increased expression in slnrx1 compared to WT. These findings suggest that SlNRX1 acts as a negative regulator of plant immunity, facilitating infection by the Psm pathogen through interference with the phytohormone SA signaling pathway. Thus, targeted mutagenesis of SlNRX1 is a promising genetic means to enhance biotic stress resistance in crop breeding.

A Tertiary Care Center's Experience with Clinicopathological Characteristics of Gallbladder Carcinoma in Our Population.

Introduction: Gallbladder cancer (GBC) is the most common malignant biliary tract tumor with the shortest survival from the time of diagnosis. This poor prognosis is due to the destructive biologic behavior of GBC, lack of sensitive screening tests for early detection, and vague nature of first presentation. Here in this study, we will evaluate the baseline characteristics of the patients presenting with gallbladder carcinoma in our population. Materials and methods: This retrospective study was conducted in the Department of Gastroenterology at Sindh Institute of Urology and Transplantation (SIUT), Karachi. Patient data were compiled and composed from the in-patient health records, radiology, and operational records. Those patients with suspicion of GBC, but negative at histology, or patients having inconclusive radiologic findings, were excluded. Baseline characteristics were recorded. Results were presented as means ± SD for quantitative data or as numbers with percentages for qualitative data. Continuous variables were analyzed using the Student's t-test, while categorical variables were analyzed using the Chi-square test. A p-value of <0.05 was considered statistically significant. Results: A total of 162 patients were included in our study. Among them, 101 (62.3%) were females. Hypertension was the most common comorbid illness noted in 29 (17.9%) patients while 91 (56.2%) patients had no concurrent comorbidities. Most common risk factor for carcinoma of gallbladder was gallstones seen in 106 (65.1%) patients. The most common presenting complaint was combination of obstructive jaundice, weight loss with right hypochondrial pain seen in 66 (40.7%) patients. On CT abdomen, direct liver infiltration without lymphovascular invasion was noted in 77 (47.5%) patients followed by liver infiltration along with lymphovascular invasion in 26 (16%) patients and distant metastasis in 24 (14.8%) patients. On gallbladder (GB) mass biopsy, 58 (35.8%) patients had well-differentiated, 46 (28.4%) had moderately differentiated, while 33 (20.4%) had poorly differentiated adenocarcinoma. Of 162 patients, 103 (63.6%) patients underwent endoscopic retrograde cholangiopancreatography (ERCP). The most common finding on ERCP was proximal common bile duct (CBD) stricture with intrahepatic biliary system dilatation which was noted in 95 (58.6%) patients. Percutaneous transhepatic cholangiography (PTC) was performed only in 9 (5.6%) patients. Seventeen (10.5%) patients were managed by simple cholecystectomy, 39 (24.1%) patients underwent extended cholecystectomy, 14 (8.6%) patients underwent chemotherapy, while 102 (56.8%) patients were given palliative management. When followed for 1 year, 101 (62.3%) patients died within 6 months. Conclusion: The baseline characteristics, biopsy findings, modes of treatment, and rates of 1 year mortality were studied in patients with gallbladder carcinoma in our population. Advanced age, high white blood cell counts, and serum bilirubin at presentation with low lymphocyte count and presence of comorbid illnesses were the factors independently associated with increased mortality in patients with gallbladder carcinoma. However, further studies with large sample size and stratification with respect to age, gender, and different variables can be done in terms of mortality in patients with gallbladder carcinoma. How to cite this article: Akbar N, Yaseen T, Muhammad A, et al. A Tertiary Care Center's Experience with Clinicopathological Characteristics of Gallbladder Carcinoma in Our Population. Euroasian J Hepato-Gastroenterol 2022;12(1):35-39.

Phytochemical, acute toxicity and renal protective appraisal of Ajuga parviflora hydromethanolic leaf extract against CCl4 induced renal injury in rats.

BACKGROUND: Degenerative kidney diseases are mostly associated with oxidative stress. Natural products are considered as the antioxidants enrich food that can restrict the progress of oxidative stress induced disorders. Therefore, the present study was aimed to evaluate the renal protective effect of Ajuga parviflora leaf extract in carbon tetrachloride intoxicated rats. METHODS: The hydromethanolic extract of A. parviflora leaves was obtained by extracting twice in 60% methanol. The principal bioactive constituents were detected by LC/MS analysis. Toxicity of plant extract was assessed using brine shrimp lethal toxicity test and acute toxicity model on healthy Sprague-Dawley male rats. Nephroprotective effects of plant extract were also evaluated on rats by inducing CCl4 renal toxicity in comparison with positive control and naïve groups. The dose of A. parviflora administered to animal was 100, 200 and 300 mg/kg. All administrations were given orally on an alternate day basis for 30 days. Urine and serum biomarkers were analyzed, along with antioxidant enzymes. Finally, the DNA damages, lipid peroxides, hydrogen peroxides and nitrites were assessed in rat's renal tissue. The histopathology alterations in renal tissues were further studied for kidney damages. RESULTS: The LC/MS analysis confirmed the presence of different important pharmacological compounds in A. parviflora methanolic leaf extract. The key bioactive compounds include pyocyanin, zonisamide, D Saccharic acid, altretamine, carbocyclic thromboxane A2, Sinapyl alcohol, and vitamin C. The important polypeptides identified include Lys-Tyr-Lys, His-His-Lys, Met-Asp-Arg, Phe-Val-Arg, and PyroGlu-Val-Arg. The LD50 of A. parviflora was found to be > 1000 µg/mL. A. parviflora administration significantly subsides CCl4 toxicity in rats, reduced the elevated level of RBCs, pus and epithelial cells. The abnormal elevated level of specific gravity, creatinine, urobilinogen, urea and albumin were also reduced to normal physiological level. The reduced urinary protein and pH were also normalized. The serum urobilinogen, urea and total bilirubin levels were also reversed to normal levels while the diminished albumin and total protein levels also came to normal. The important phase I and II enzyme levels were also reversed in A. parviflora administered rats. The H2O2, thiobarbituric acid reactive substance (TBARS) and nitrite levels were significantly decreased. Furthermore, the damaged DNA and histopathological changes in CCl4 exposed rats were also highly significantly reversed after the administration of A. parviflora. All effects were significant (P < 0.05) and highly significant (P < 0.005) at 100 and 300 mg/kg respectively. CONCLUSION: The restored urine and serum profile of various parameters to normal physiological levels suggests that the A. parviflora has potential antioxidant and repairing potential in renal disorders.

Design and development of lipid modified chitosan containing muco-adhesive self-emulsifying drug delivery systems for cefixime oral delivery.

Current study was aimed to design and develop muco-adhesive self-nano emulsifying drug delivery system (SNEDDs) for improved pharmacokinetics of Cefixime (CFX) in rabbits. The components of SNEDDs formulation i.e., cinnamon oil, Tween® 80, and PEG 200 as oil, surfactant, and co-surfactant respectively were selected based on their high solubilizing capability of the drug. SNEDDs formulation was optimized using Design of experiments (D-optimal design) in terms of droplet size, poly dispersity index and zeta potential. The optimized SNEDDs formulation was studied for various parameters like droplet size, morphology, zeta potential, emulsification, optical clarity, thermodynamic stability, GIT stability, and robustness to dilution. CFX was loaded to optimized formulation to form CFX-SNEDDs. Furthermore, acyl-chitosan, a muco-adhesive agent, was added to CFX-SNEDDS to prepare CHT-CFX-SNEDDS. In vitro drug release showed the controlled release behavior reached a maximum value of 70 % at pH 6.8 within 24 h. The droplet size, atomic force microscopy, and optical clarity analysis revealed the formation of nanosized emulsion (156 ± 25 nm) with spherical morphology. Also in vivo pharmacokinetic studies on rabbits showed an increased drug plasma concentration for CHT-CFX-SNEDDs (15 ± 3 µg/mL) and CFX-SNEDDs (9 ± 2 µg/mL) in comparison with control CFX (4 ± 1 µg/mL). The results indicated that the developed CHT-CFX-SNEDDs with an increased degree of solubilization, permeation, and nanosized range emulsion enhance the oral performance of CFX.

Synthesis, characterization and drug delivery application of Dapsone based double tailed biocompatible nonionic surfactant.

The increase in antimicrobial resistance has created a crisis that has become top priority for global policy and public health. Antibiotics are constantly being rendered in-effective due to the emergence of bacterial resistance; therefore, novel strategies for improving therapeutic efficacies of existing drugs must be focused. Advancements in nanotechnology have opened up new avenues for enhancing therapeutic efficacy of existing drugs via construction of intelligent and efficient delivery systems. This study reports the synthesis of Dapsone based nonionic surfactant and its utilization as delivery system for Ceftriaxone sodium. The synthesized nonionic surfactant was characterized via mass spectrometry and 1H NMR and IR spectroscopic techniques. The drug loaded vesicles of newly synthesized sulfur based nonionic were formed through thin film hydration method and characterized for drug entrapment efficiency, vesicles size, zeta potential, morphology using UV-vis spectrometry, dynamic light scattering (DLS) and atomic force microscopic (AFM) techniques. The biocompatibility of newly synthesized surfactant was assessed using blood hemolysis and in-vitro cells cytotoxicity. Antibacterial potential of drug loaded vesicles was assessed in gram positive and gram negative bacterial cultures. The spectroscopic results confirm successful synthesis of novel sulfur based nonionic surfactant that formed spherical shaped drug loaded vesicles with an average size of 97.95 ± 3.45 nm and 56.3 ± 3.15 % entrapment of the model drug (Ceftriaxone sodium). The vesicles displayed negative surface charge of -16.8 ± 3.72 mV and released the entrapped drug in a controlled way in-vitro drug release. The drug loaded vesicular formulation showed enhanced cellular uptake and greater antibacterial potentials when compared with control. Results of this study show that the Dapsone based surfactant is safe, biocompatible, non-toxic and can be used as promising vesicular carrier for enhancing therapeutic efficacy of antibacterial drug, Ceftriaxone sodium.

Synthesis of biocompatible triazole based non-ionic surfactant and its vesicular drug delivery investigation.

Numerous nanotechnological approaches have been widely practiced to improve the bioavailability of less aqueous soluble drugs; phospholipid based vesicles (liposomes) being the most widely applied drug delivery system. However; due to stability issues, large scale production limitations, sterilization and long term storage problems; non-ionic surfactant based vesicles (niosomes) are considered their excellent counterparts. Niosomes are vesicles of non-ionic surfactants having the ability to carrying both hydrophilic and hydrophobic drugs in their inner aqueous or lipid bilayer compartments. In this research work, triazole based non-ionic surfactant (TBNIS) was synthesized and characterized by different spectroscopic techniques and then screened for biocompatibility using NIH 3T3 cell line, blood hemolysis assay and acute toxicity in mice. The synthesized surfactant was then checked for niosomes' formation, Amphotericin B loading and entrapment efficiency, drug release, stability and bioavailability of the drug was assessed and compared with free drug solution. The synthesized surfactant was found biocompatible and caused less blood hemolysis, greater cell vial ability and negligible toxicity in animals. The size of drug loaded niosomal vesicles of TBNIS based surfactant was 179.9 ± 3.23 nm with smaller size distribution i.e. 0.29 ± 0.02. The triazole based surfactant vesicles showed 88.76 ± 3.45 % drug entrapment efficiency, sustained drug release profile and stability. The drug in TBNIS based vesicles has greater oral bioavailability 0.099 ± 0.03 as compared to plan drug solution 0.012 ± 0.023 µg/mL. Results of this study suggests that the newly synthesized triazole based surfactant can be used in drug delivery for improving bioavailability of less water soluble drugs like Amphotericin B.