Modulation of immune cum inflammatory pathway by earthworm granulation tissue extract in wound healing of diabetic rabbit model.

Regeneration is a rare occurrence in the animal kingdom, but the earthworm stands out as a remarkable example of this phenomenon. Recent research has highlighted the promising wound healing properties of extracts derived from earthworms. Therefore, we propose that earthworm granulation tissue extract (EGTE) may facilitate wound healing by regulating immune responses in a rabbit diabetic wound model. Electron microscopy reveals that 70 % EGTE possesses noteworthy porosity with spherical to irregularly oval configuration. Gas chromatography-mass spectrometry (GC-MS) Characterization of EGTE revealed higher levels of ergosta-5,7,22-trien-3-ol, (3. beta.,22E). In-Vitro studies revealed significant anti-oxidant, anti-inflammatory and anti-bacterial properties in dose dependent manner. Likewise, cytotoxicity assessments reveal that 70 % EGTE exhibits minimal harm to cells while displaying substantial antioxidant and anti-inflammatory activities. For In-Vivo studies excision wounds were created on the dorsal regions of the experimental animals and were divided as Group I (50 % EGTE), Group II (70 % EGTE), Group III (vehicle) and Group IV (distilled water). Over a 21-day observation period 70 % EGTE facilitated the early healing of wounds in the experimental animals, evident through prompt wound closure, granulation tissue formation, increased DNA content, enhanced tensile strength of the wound area and enhanced the expression/synthesis of wound healing markers/proteins. From these results it can be postulated that EGTE accelerates wound healing by immune modulation, dampening of inflammatory pathway and enhanced expression of growth markers. Henceforth making it promising candidate for therapeutic use in diabetic wound healing.

Nanocomposites of iron oxide, sodium alginate, and eugenol induce apoptosis via PI3K/Akt/mTOR signaling in Hep3 cells and in vivo hepatotoxicity in the zebrafish model.

Hepatic cancer is among the most recurrently detected malignancies worldwide and one of the main contributors to cancer-associated mortality. With few available therapeutic choices, there is an instant necessity to explore suitable options. In this aspect, Nanotechnology has been employed to explore prospective chemotherapeutic approaches, especially for cancer treatment. Nanotechnology is concerned with the biological and physical properties of nanoparticles in the therapeutic use of drugs. In the current work, formulation, and characterization of α-Fe2O3-Sodium Alginate-Eugenol nanocomposites (FSE NCs) using several approaches like SEM and TEM, UV-visible, FTIR, and PL spectroscopy, XRD, EDAX, and DLS studies have been performed. With an average size of 50 nm, the rhombohedral structure of NCs was identified. Further, their anticancer activity against Hep3B liver cancer cell lines has been performed by cell viability, dual staining, DCFH-DA, Annexin-V/-FITC/PI, cell cycle analysis methods, and PI3K/Akt/mTOR signaling proteins were studied to assess the anticancer effects of the NCs in Hep3B cells. Also, anti-cancer activity on animal modeling in-vivo using zebra fishes to hematological parameters, liver enzymes, and histopathology study effectiveness was noticed. Moreover, the NCs reduced the viability, elevated the ROS accumulation, diminished the membrane integrity, reduced the antioxidants, blocked the cell cycle, and triggered the PI3K/Akt/mTOR signaling axis that eventually resulted in cell death. As a result, FSE NCs possess huge potential for use as a possible anticancer candidate.

Syzygium cumini (L.) Extract-Derived Green Titanium Dioxide Nanoparticles Induce Caspase-Dependent Apoptosis in Hepatic Cancer Cells.

An aqueous extract of Syzygium cumini seeds was utilized to green synthesize titanium dioxide nanoparticles (TiO2 NPs). UV-Visible, DLS, FTIR, XRD, FESEM, TEM, SAED, EDAX, and photoluminescence spectroscopy techniques were employed to characterize the prepared TiO2 nanoparticles. The rutile crystal structure of TiO2 NPs was revealed by XRD study. The TEM and FESEM images of the TiO2 NPs revealed an average particle size of 50-100 nm. We employed EDAX to investigate the elemental compositions of TiO2 NPs. The O-Ti-O stretching bands appeared in the FTIR spectrum of TiO2 NPs at wavenumbers of 495 cm-1. The absorption edge peaks of TiO2 NPs were found in the UV-vis spectra at 397 nm. The MTT study revealed that TiO2 NPs effectively inhibited the growth of liver cancer Hep3 and Hep-G2 cells. The results of the corresponding fluorescent staining assays showed that TiO2 NPs significantly increased ROS generation, decreased MMP, and induced apoptosis in both liver cancer Hep3 and Hep-G2 cells. TiO2 nanoparticles lessened SOD, CAT, and GSH levels while augmenting MDA contents in Hep3 and Hep-G2 cells. In both Hep3 and Hep-G2 cells treated with TiO2 NPs, the Bax, CytC, p53, caspase-3, -8, and -9 expressions were remarkably augmented, while Bcl-2 expression was reduced. Overall, these findings revealed that formulated TiO2 NPs treatment considerably inhibited growth and triggered apoptosis in Hep3 and HepG2 cells.

Pluronic-F-127-Passivated SnO2 Nanoparticles Derived by Using Polygonum cuspidatum Root Extract: Synthesis, Characterization, and Anticancer Properties.

Nanotechnology has emerged as the most popular research topic with revolutionary applications across all scientific disciplines. Tin oxide (SnO2) has been gaining considerable attention lately owing to its intriguing features, which can be enhanced by its synthesis in the nanoscale range. The establishment of a cost-efficient and ecologically friendly procedure for its production is the result of growing concerns about human well-being. The novelty and significance of this study lie in the fact that the synthesized SnO2 nanoparticles have been tailored to have specific properties, such as size and morphology. These properties are crucial for their applications. Moreover, this study provides insights into the synthesis process of SnO2 nanoparticles, which can be useful for developing efficient and cost-effective methods for large-scale production. In the current study, green Pluronic-coated SnO2 nanoparticles (NPs) utilizing the root extracts of Polygonum cuspidatum have been formulated and characterized by several methods such as UV-visible, Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray (EDAX), transmission electron microscope (TEM), field emission-scanning electron microscope (FE-SEM), X-ray diffraction (XRD), photoluminescence (PL), and dynamic light scattering (DLS) studies. The crystallite size of SnO2 NPs was estimated to be 45 nm, and a tetragonal rutile-type crystalline structure was observed. FESEM analysis validated the NPs' spherical structure. The cytotoxic potential of the NPs against HepG2 cells was assessed using the in vitro MTT assay. The apoptotic efficiency of the NPs was evaluated using a dual-staining approach. The NPs revealed substantial cytotoxic effects against HepG2 cells but failed to exhibit cytotoxicity in different liver cell lines. Furthermore, dual staining and flow cytometry studies revealed higher apoptosis in NP-treated HepG2 cells. Nanoparticle treatment also inhibited the cell cycle at G0/G1 stage. It increased oxidative stress and promoted apoptosis by encouraging pro-apoptotic protein expression in HepG2 cells. NP treatment effectively blocked the PI3K/Akt/mTOR axis in HepG2 cells. Thus, green Pluronic-F-127-coated SnO2 NPs exhibits enormous efficiency to be utilized as an talented anticancer agent.

The Regularity of the Site of Impaction in Recurrent Gallstone Ileus: A Systematic Review and Meta-Analysis of Reported Cases.

Objective: Due to the rarity of recurrent gallstone ileus (RGSI), its epidemiological and clinical features are elusive. With a focus on mortality and the site of impaction, this study consolidates the key clinical characteristics of index GSI (IGSI) and RGSI. Methods: A meta-analysis of cases reported on RGSI was performed. Risk factors for mortality and site of impaction were examined, and a subgroup analysis was performed for age, sex, and site of impaction (jejunum, ileum, or others). Results: In the final analysis, 50 (56 individual cases) studies were included. The paired data for the site of impaction was available for 45 patients. Women accounted for 87.3% of all RGSI cases included in the pooled analysis. The median age (interquartile range, IQR) of the patients was 70 (63-76) years, and the median time of recurrence (IQR) was 20.5 (8.5-95.5) days. The overall mortality rate was 11.8%, without correlation between the mortality rate and age, the time of recurrence, or the site of impaction. The region in which the stone was found in RGSI and IGSI was similar in most cases (p=0.002). Logistic regression also revealed a higher probability of stone impaction in the ileum in RGSI if it was the site of impaction in IGSI. In most cases, enterolithotomy was the preferred method. Conclusions: A high index of suspicion for RGSI should be maintained for older women with a history of GSI. The region where the stone was impacted during IGSI should be investigated first in such patients.

Identification of RPL5 gene variants and the risk of hepatic vein thrombosis in Saudi patients.

OBJECTIVES: To identify ribosome protein L5 gene variants and the risk of hepatic vein thrombosis in Saudi patients. METHODS: A case-control study was conducted during the period of May 2018 to September 2019. Sixty-five patient cases of hepatic vein thrombosis (HVT) were chosen, and 50 healthy individuals of the same ages and both gender were set as a control group. The genotype of the gene RPL5 was determined by PCR please provide abbreviation in full and capillary electrophoresis. Sanger sequencing for genetically screened variants was applied for the RPL5 gene. RESULTS: Alleles A at variant rs182018447 and T allele at variant rs559377519 were strongly corelated (p=0.009 and p=0.037, respectively) with the risk of HVT. The genotype frequencies of the RPL5 gene, the A/A genotypes at rs182018447 and T/T at rs559377519 were associated with HVT (p=0.000 and p=0.004; respectively) and an increase in risk for HVT among these patients. Please rephrase the highlighted text without using the word respectively. CONCLUSION: Our findings indicate that the 5 genetic novel variants examined in the RPL5 gene were associated with a risk of HVT in all our Saudi cases. Additionally, the A/A at rs182018447 and T/T at rs559377519 genotypes were substantially susceptible to HVT in all these patients.

Genetic Variants of RPL5 and RPL9 Genes among Saudi Patients Diagnosed with Thrombosis.

BACKGROUND: Thrombosis directly affects the quality of life with increased mortality. The RPL5 (L5) gene on intron 6 on chromosome 1p22, rs6604026 is associated with multiple sclerosis risk, whereas RPL9 (L9) on 8 exons on chromosome 4p14 has been documented so far as being an essential involvement in the proliferation of protein synthesized cells mostly by gene products. OBJECTIVE: The aim of this work was to assess genetic variants of RPL5 and RPL9 and thrombosis to characterize their role in the diagnosis of thrombosis among the Saudi population. METHODS: The cross-sectional study involved 100 Saudi patients diagnosed with thrombosis (arterial or venous) in 50 healthy individuals as controls in the same age and sex groups. Primers were designed RPL5 and RPL9 for molecular analysis. The Sanger System ABI-3730xL (Hong Kong) automatic sequencing was used for DNA sequencing. Statistical analysis was performed using the Prism 5 and SPSS version-21 programs. RESULTS: The male / female age ratio was 66.7 / 57.4, and the mean age was 61.2 years. Most of the patients were self-identifiable and without a previous history of thrombosis (61.0%). Most of the patients had just been diagnosed, that is, in the last five years (74.0%), about 43% of the patients underwent treatment using combination therapy (Aspirin and oral anticoagulants). New gene variants of RPL5 (5 SNPs) and RPL9 (9 SNPs) were detected in Saudi thrombotic patients. CONCLUSION: Mutations in RPL5 and RPL9 were reported in all thrombotic patients, represented by a new variant of the ribosomal protein gene and correlated with thrombosis in the Saudi population. These results may reflect an association between the ribosomal protein SNP gene and the incidence and progression of thrombosis in the Saudi population.

Inverse correlation between biofilm production efficiency and antimicrobial resistance in clinical isolates of Pseudomonas aeruginosa.

This study assessed the correlation between biofilm formation in Pseudomonas aeruginosa strains with both the level of antibiotic resistance, and the number of virulence- and biofilm-related genes encoded. A total of sixty-six, non-replicate and prospectively collected P. aeruginosa strains were identified and tested. Potential ampD mutations that may impose resistance to extended-spectrum ß-lactam (ESBL) agents were further explored. Of the sixty-six tested isolates, 40 demonstrated the multidrug resistance (MDR) phenotype, while twenty-six were non-MDR strains. An inverse correlation was observed between antibiotic resistance and the potential capacity to form biofilms. In addition, no correlation was observed between novel ampD mutations and the tendency for MDR isolates to acquire a ß-lactam-resistant phenotype. The present study emphasizes the need for enhanced infection preventive measures in various hospital units, since both MDR and non-MDR P. aeruginosa isolates exhibited a high level of biofilm-forming capacity and the presence of virulence-associated genes.

Biofilm-Formation in Clonally Unrelated Multidrug-Resistant Acinetobacter baumannii Isolates.

This study analyzed the genotype, antibiotic resistance, and biofilm formation of Acinetobacter baumannii strains and assessed the correlation between biofilm formation, antibiotic resistance, and biofilm-related risk factors. A total of 207 non-replicate multi-drug-resistant A. baumannii strains were prospectively isolated. Phenotypic identification and antimicrobial susceptibility testing were carried out. Isolate biofilm formation ability was evaluated using the tissue culture plate (TCP), Congo red agar, and tube methods. Clonal relatedness between the strains was assessed by enterobacterial repetitive intergenic consensus-PCR genotyping. Of the 207 isolates, 52.5% originated from an intensive care unit setting, and pan resistance was observed against ceftazidime and cefepime, with elevated resistance (99-94%) to piperacillin/tazobactam, imipenem, levofloxacin, and ciprofloxacin. alongside high susceptibility to tigecycline (97.8%). The Tissue culture plate, Tube method, and Congo red agar methods revealed that 53.6%, 20.8%, and 2.7% of the strains were strong biofilm producers, respectively, while a significant correlation was observed between biofilm formation and device-originating respiratory isolates (p = 0.0009) and between biofilm formation in colonized vs. true infection isolates (p = 0.0001). No correlation was detected between antibiotic resistance and biofilm formation capacity, and the majority of isolates were clonally unrelated. These findings highlight the urgent need for implementing strict infection control measures in clinical settings.

Genetic Diversity of Imipenem-Resistant Acinetobacter baumannii Infections at an Intensive Care Unit.

Introduction. Imipenem-resistant Acinetobacter baumannii (IRAB) represents a major clinical threat. Dissemination in critical care areas necessitates effective action measures including genotyping tools to study the clonality of these strains and trace their origin. The main aim of this study is to assess the genetic relatedness between IRAB isolates in our institution intensive care units (ICU) which are at a particular risk of outbreaks. METHODS: Nonreplicate IRAB strains were serially collected over 3 years period (January 2016-December 2018) from patients admitted to the ICU. The isolates were phenotypically identified by a matrix-assisted laser desorption/ionization time-of-flight- (MALDI-TOF-) based system (VITEK MS), and their susceptibility was tested by the phenotypic-based VITEK 2 system. Molecular fingerprinting was performed by enterobacterial repetitive intergenic consensus (ERIC-PCR) followed by hierarchal clustering. The patterns were analysed by the software of BioNumerics package version 7.6.3 (Applied Maths, Belgium). RESULTS: A total of eighty IRAB were isolated from 31 colonization and 59 infection sites in patients admitted to the ICU. Sixty-two samples were respiratory in origin (77.5%). The generated dendrogram revealed distinct patterns for majority (95%) of the strains. Meropenem maintained activity against 43.8% of the imipenem-resistant A. baumannii. CONCLUSION: Meropenem can be a therapeutic option for imipenem-resistant A. baumannii.

The genetics of amyotrophic lateral sclerosis: current insights.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that results in loss of the upper and lower motor neurons from motor cortex, brainstem, and spinal cord. While the majority of cases are sporadic, approximately 10% show familial inheritance. ALS is usually inherited in an autosomal dominant manner, although autosomal recessive and X-linked inheritance do occur. To date, 24 of the genes at 26 loci have been identified; these include loci linked to ALS and to frontotemporal dementia-ALS, where family pedigrees contain individuals with frontotemporal dementia with/without ALS. The most commonly established genetic causes of familial ALS (FALS) to date are the presence of a hexanucleotide repeat expansion in the C9ORF72 gene (39.3% FALS) and mutation of SOD1, TARDBP, and FUS, with frequencies of 12%-23.5%, 5%, and 4.1%, respectively. However, with the increasing use of next-generation sequencing of small family pedigrees, this has led to an increasing number of genes being associated with ALS. This review provides a comprehensive review on the genetics of ALS and an update of the pathogenic mechanisms associated with these genes. Commonly implicated pathways have been established, including RNA processing, the protein degradation pathways of autophagy and ubiquitin-proteasome system, as well as protein trafficking and cytoskeletal function. Elucidating the role genetics plays in both FALS and sporadic ALS is essential for understanding the subsequent cellular dysregulation that leads to motor neuron loss, in order to develop future effective therapeutic strategies.