In-vitro Evaluation of Wild Bitter Melon (Momordica charantia) Extracts against Periodontopathic Bacteria (Prevotella intermedia and Porphyromonas gingivalis) using Antibacterial, Anti-Inflammatory and Molecular Docking Analysis.

Wild bitter melon (Momordica charantia) extracts were prepared and their antibacterial and anti-biofilm assay were investigated against two different periodontopathic bacteria (Prevotella intermedia and Porphyromonas gingivalis) for the first time to the best of our knowledge based on the presence of different phytochemical compounds. Momordica charantia solvent extracts were prepared and phytochemical analysis was performed. Minimal inhibitory and bactericidal concentrations were determined. Antibacterial activity was evaluated using the standard well diffusion method. Anti-inflammatory studies on periodontal ligament (PDL) cell viability and lipopolysaccharide (LPS)-induced inflammation were performed. Molecular docking was investigated between the bioactive compound (Charantadiol A) of plant extract and biofilm-expressing genes in each test organism. Phytochemicals from ethanol extract showed promising results; alkaloids, flavonoids, phenols, and tannins were found present at considerable levels. The minimum inhibitory concentration was found to be 400 µg/mL for Prevotella intermedia and Porphyromonas gingivalis. Antibacterial activity expressed in terms of zone of inhibition showed 14 mm to 18 mm zones against the test organisms. The molecular docking report revealed the maximum binding energy of about -6.54 Kcal/Mol of binding energy between Charantadiol A and fimA of Porphyromonas gingivalis. Anti-biofilm study showed that the minimum biofilm eradication concentration (MBEC) of Momordica charantia expressed significantly good results against the test organisms. The PDL cell viability values expressed in percentage indicated the anti-inflammatory properties of Momordica charantia extracts at three different known concentrations. The findings concluded that Momordica charantia extracts have promising prospects as an anti-periodontopathic and anti-inflammatory agent.

In silico-designed antimicrobial peptide targeting MRSA and E. coli with antibacterial and antibiofilm actions.

Antibiotic resistance is a paramount global health issue, with numerous bacterial strains continually fortifying their resistance against diverse antibiotics. This surge in resistance levels primarily stems from the overuse and misuse of antibiotics in human, animal, and environmental contexts. In this study, we advocate for exploring alternative molecules exhibiting antibacterial properties to counteract the escalating antibiotic resistance. We identified a synthetic antimicrobial peptide (AMP) by using computational search in AMP public databases and further engineering through molecular docking and dynamics. Microbiological evaluation, cytotoxicity, genotoycity, and hemolysis experiments were then performed. The designed AMP underwent rigorous testing for antibacterial and antibiofilm activities against Methicillin-Resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), representing gram-positive and gram-negative bacteria, respectively. Subsequently, the safety profile of the AMP was assessed in vitro using human fibroblast cells and a human blood sample. The selected AMP demonstrated robust antibacterial and antibiofilm efficacy against MRSA and E. coli, with an added assurance of non-cytotoxicity and non-genotoxicity towards human fibroblasts. Also, the AMP did not demonstrate any hemolytic activity. Our findings emphasize the considerable promise of the AMP as a viable alternative antibacterial agent, showcasing its potential to combat antibiotic resistance effectively.

DNA barcoding, phylogeography and evolutionary dynamics of Chrysichthys auratus.

This study embarked on an exploration into the genetic structure and evolutionary history of the Chrysichthys auratus species, leveraging PCR amplification, phylogenetic trees, and haplotype networks. Specific DNA segments were successfully amplified and visualized through electrophoresis. Newly obtained sequences were Bank into GenBank and given accession numbers (OR730807-OR730808-OR730809). The Neighbor-Joining method provided insights into the evolutionary relationships among taxa, further augmented by bootstrap values and the Tamura 3-parameter method. A comprehensive geographical haplotype network showcased pronounced genetic differentiation, especially between remote populations. Nonetheless, shared haplotypes between proximate regions indicated either ancestral genetic connections or ongoing gene flow. Employing the COI-DNA barcodes, an in-depth understanding of intra- and inter-populational genetic diversity was achieved. The study's findings unravel the intricate genetic landscape and evolutionary dynamics of C. auratus, offering novel perspectives into its demographic history across its vast native habitat.

Successful Late Repair of Truncus Arteriosus: A Single Center Experience.

Background: Truncus arteriosus is a rare congenital heart defect resulting from the failure of the truncus arteriosus to divide during fetal development. It leads to a single outflow tract from the heart and, if left untreated, can be fatal. Late presentation and repair can also increase the risk of pulmonary hypertensive crises, which can lead to morbidity and mortality after repair. Methods: We performed a retrospective study examining outcomes of late-presenting patients who were repaired for this anomaly at our institution. Results: We identified seven patients who underwent late repair of truncus arteriosus who were 3 to 11 years of age. There were six females and one male. Postoperatively, all patients showed improvement in symptoms and hemodynamic parameters, with no reported mortality. The median duration of stay in the intensive care unit was nine days and with a range from 3 to 18 days, while the median hospital stay was 29 days with a range from 21 to 60 days. Conclusion: These findings highlight the potential for successful outcomes even in cases of delayed diagnosis.

A novel triad for the diagnosis of endometriosis, the short anogenital distance combines with high endometrial BCL2 and low endometrial FASL.

OBJECTIVE: To investigate the anogenital distance from the upper verge of the anus to the posterior fourchette (AGDAF), FASL, and BCL2 combination as a reliable and non-invasive tool for the diagnosis of endometriosis. METHODS: This study included 100 women with endometriosis and 50 women without endometriosis as the control group. All cases underwent history taking, body mass index (BMI) measurement, AGD measurement, and FASL and BCL2 immunohistochemical staining of the eutopic endometrial tissue. RESULTS: This study included 150 women divided into endometriosis and control groups. Endometriosis cases significantly had shorter AGDAF, 22.9 ± 2.6 mm, compared with the control group, 27.3 ± 3.5 mm (P < 0.001). Lower FASL and higher BCL2 expression were associated with endometriosis (P < 0.001). The combined measurement of AGDAF (cut-off point 24.55 mm) with FASL and BCL2 was associated with endometriosis (P < 0.001). The combined diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of AGDAF, FASL, and BCL2 were 83%, 78%, 87.3%, and 69.6%, respectively. The area under the curve was greater for AGDAF, FASL, and BCL2 in combination than for individual measurements. CONCLUSION: Combining short AGDAF with high BCL2 and low FASL is a highly sensitive, non-invasive diagnostic tool for endometriosis.

Acute Kidney Injury Among COVID-19-Positive Patients Is Associated With Higher Mortality: A Single-Center Experience.

OBJECTIVES: Renal complications of COVID-19 are not yet well studied. We aimed to evaluate acute kidney injury prevalence among hospitalized patients with COVID-19 infection and explore its effect on patient outcomes. MATERIALS AND METHODS: We retrospectively evaluated 586 hospitalized patients with COVID-19. Of these patients, 267 (45.5%) developed acute kidney injury, as classified according to the Kidney Disease Improving Global Outcomes guidelines. We compared this group with 319 patients (54.5%) without acute kidney injury. RESULTS: Most patients in both study groups were men; mean age was 60.8 ± 14 versus 51.7 ± 16 years. Comorbid conditions that were substantially predominant among patients with acute kidney injury were diabetes mellitus (64% vs 42.9%), hypertension (72.6% vs 43.5%), and ischemic heart disease (25% vs 14.7%). Fever, cough, shortness of breath, and dehydration were the main presentations among patients with acute kidney injury, and patients in this group had greater prevalence of radiological findings concordant with COVID-19 (86.8% vs 59.8%). Sepsis, volume depletion, shock, arrhythmias, and acute respiratory distress syndrome were higher in patients with acute kidney injury. Anticoagulation (85% vs 59.2%), vasopressors, plasma infusions, antimicrobials, and steroids were more frequently used in patients with acute kidney injury. More patients with acute kidney injury had acute respiratory failure requiring mechanical ventilation (62.3% vs 32.9%), with higher overall mortality rate (63.2% vs 31.1%). CONCLUSIONS: We found more frequent prevalence of acute kidney injury associated with severe COVID-19 than shown in reports from Chinese, European, and North American cohorts. Patients with COVID-19 who developed acute kidney injury had risk factors such as hypertension and diabetes, greater need for mechanical ventilation, were males, and were older age. Mortality was high in this population, especially among older patients and those who developed Kidney Disease Improving Global Outcomes stage 3 disease.

Design and development of a portable low-cost QCM-based system for liquid biosensing.

Quartz crystal microbalance (QCM) is a versatile sensing platform that has gained increasing attention for its use in bioapplications due to its high sensitivity, real-time measurement capabilities, and label-free detection. This article presents a portable QCM system for liquid biosensing that uses a modified Hartley oscillator to drive 14 mm-diameter commercial QCM sensors. The system is designed to be low-cost, easy to use, and highly sensitive, making it ideal for various bioapplications. A new flow cell design to deliver samples to the surface of the sensor has been designed, fabricated, and tested. For portability and miniaturization purposes, a micropump-based pumping system is used in the current system. The system has a built-in temperature controller allowing for accurate frequency measurements. In addition, the system can be used in benchtop mode. The capability of the present system to be used in liquid biosensing is demonstrated through an experimental test for sensitivity to changes in the viscosity of glycerol samples. It was found to have a sensitivity of 263.51 Hz/mPa.s using a 10 MHz QCM sensor. Future work regarding potential applications was suggested.

Assessment of crestal bone loss and periodontal parameters of polymer infiltrated ceramic network versus lithium disilicate implant hybrid abutment crowns in the esthetic zone (A randomized clinical trial).

BACKGROUND: Lithium disilicate can be reliable when restoring implants in the esthetic zone. However, it has a high elastic modulus. This might increase the amount of forces transmitted to the crestal bone. AIM OF THE STUDY: To evaluate the crestal bone loss and peri-implant periodontal parameters of polymer infiltrated ceramic network compared to lithium disilicate implant-supported hybrid abutment crowns after 12 months of follow-up. METHODOLOGY: 44 patients were enrolled. They were randomly assigned into two groups (n = 22). The first group received 22 implants restored with polymer-infiltrated ceramic network (Vitaenamic) hybrid abutment crowns. The second group received 22 implants restored with lithium disilicate (e.max) hybrid abutment crowns over immediately placed implants in the esthetic zone. Periapical radiographs were taken immediately after prosthetic placement and 1 year later utilizing a parallel technique, to assess crestal bone loss. Periodontal parameters were assessed after 1 year. RESULTS: Regarding crestal bone loss, a comparison between group I (Vitaenamic) and group II (e.max) was made by using an Independent t-test, which showed an insignificant difference between them (p > 0.05). A comparison between groups I and II revealed insignificant differences regarding periodontal parameters (probing depth, bleeding on probing, visible plaque, and suppuration). CONCLUSIONS: Regarding bone stability and periodontal parameters, polymer infiltrated ceramic network and lithium disilicate hybrid abutment crowns showed comparable results. Both materials showed clinically acceptable hard and soft tissue responses.

Role of Cannabinoid Type 2 Receptor Activation in Renal Fibrosis Induced by Unilateral Ureteric Obstruction in Rats.

Background: Chronic kidney disease (CKD) ends mostly with renal fibrosis. The effect of CB2 receptor on renal fibrosis has been unclear. The aim of this study was to investigate the effect of CB2 receptor on renal fibrosis and the mechanisms behind it. Methods: 50 adult male Sprague-Dawley rats were divided into 5 groups; normal, sham; rats had their ureters only manipulated, UUO; rats had their left ureters ligated, and JWH post; rats had their left ureters ligated and they received JWH 133 for 14 days, JWH pre+post; rats received JWH 133 for 14 days before and after UUO procedure. Serum creatinine and BUN were assessed together with tissue MDA, GSH, and catalase. Histopathological evaluation of the renal tissue by H&E and Masson's trichrome was done. Immunohistochemical staining for TGF-ß1, AQP1, Caspase-3, LC3B and p62 was performed. AQP1 and CB2 receptors genes expression was detected by quantitative RT-PCR. Results: UUO had caused severe damage in the renal tissue with reduction of the renal function parameter accompanied by increase in the collagen deposition with increase TGF-ß1 and decrease AQP1 expression. Conclusions: The improvement of these parameters with JWH-133 suggests an anti-fibrotic role of CB2 receptor activation through reduction of oxidative stress, apoptosis, and autophagy.

Expert opinion on management of moderate-to-severe atopic dermatitis in Qatar.

Atopic dermatitis (AD), a chronic-relapsing inflammatory skin disorder, manifests with intense itching and eczematous lesions impairing quality of life. A heterogeneous population, and regional clinical practices for treating AD warrant the development of guidelines in Qatar. Therefore, guidelines for the management of moderate-to-severe AD in Qatar have been developed and discussed. Experts, including dermatologists and immunologists, used the Delphi technique for developing guidelines. Consensus was defined as ≥75% agreement or disagreement. AD is highly prevalent in primary and tertiary dermatology centers. AD-associated foot eczema and psoriasiform eczema are more frequent in Qatar than in Europe or USA. SCORing Atopic Dermatitis Index quantifies disease severity and itch. Dermatology Life Quality Index assesses the quality of life. Atopic Dermatitis Control Tool assesses long-term disease control. Moderate-severe AD benefits from new topicals like Janus-kinase-inhibitors or PDE4-inhibitors combined with phototherapy. Currently approved systemic agents are dupilumab, baricitinib, abrocitinib, and upadacitinib. New anti-IL-13 and anti-IL-31 therapies will soon be available. Patient education, allergy testing, and comorbidity consideration are critical in the management of AD. The expert panel established a comprehensive and pragmatic approach to managing moderate-to-severe AD, thereby assisting clinical decision-making for healthcare professionals in Qatar.

Fabrication of Spiral Low-Cost Microchannel with Trapezoidal Cross Section for Cell Separation Using a Grayscale Approach.

Trapezoidal cross-sectional spiral microfluidic channels showed high resolution and throughput in cell separation in bio-applications. The main challenges are the complexity and high cost of the fabrication process of trapezoidal cross-sectional channels on the micro-scale. In this work, we present the application of grayscale in microfluidic channel design to overcome the complexity of the fabrication process. We also use direct engraving with a CO2 laser beam on polymethyl methacrylate (PMMA) material to drastically reduce the microfluidic chip's cost (to <30 cents) and fabrication time (to 20 min). The capability of the present fabrication methodology for cell sorting applications is demonstrated through experimental tests for the separation of white blood cells (WBCs) from whole blood at different dilution factors. The experimental results indicated that an 800 µL/min flow rate provided the optimal separation efficiency using the fabricated chip. A 90.14% separation efficiency at 1% hematocrit diluted blood sample was reported.

(R,R)-BD-AcAc2 Mitigates Chronic Colitis in Rats: A Promising Multi-Pronged Approach Modulating Inflammasome Activity, Autophagy, and Pyroptosis.

Ulcerative colitis is a chronic and incurable form of inflammatory bowel disease that can increase the risk of colitis-associated cancer and mortality. Limited treatment options are available for this condition, and the existing ones often come with non-tolerable adverse effects. This study is the first to examine the potential benefits of consuming (R,R)-BD-AcAc2, a type of ketone ester (KE), and intermittent fasting in treating chronic colitis induced by dextran sodium sulfate (DSS) in rats. We selected both protocols to enhance the levels of ß-hydroxybutyrate, mimicking a state of nutritional ketosis and early ketosis, respectively. Our findings revealed that only the former protocol, consuming the KE, improved disease activity and the macroscopic and microscopic features of the colon while reducing inflammation scores. Additionally, the KE counteracted the DSS-induced decrease in the percentage of weight change, reduced the colonic weight-to-length ratio, and increased the survival rate of DSS-insulted rats. KE also showed potential antioxidant activities and improved the gut microbiome composition. Moreover, consuming KE increased the levels of tight junction proteins that protect against leaky gut and exhibited anti-inflammatory properties by reducing proinflammatory cytokine production. These effects were attributed to inhibiting NFκB and NLRP3 inflammasome activation and restraining pyroptosis and apoptosis while enhancing autophagy as revealed by reduced p62 and increased BECN1. Furthermore, the KE may have a positive impact on maintaining a healthy microbiome. To conclude, the potential clinical implications of our findings are promising, as (R,R)-BD-AcAc2 has a greater safety profile and can be easily translated to human subjects.

Involvement of glyphosate in disruption of biotransformation P450 enzymes and hepatic lipid metabolism in chicken.

The current study investigated the potentially harmful consequences of pure glyphosate or Roundup® on CYP family members and lipid metabolism in newly hatched chicks. On the sixth day, 225 fertilized eggs were randomly divided into three treatments: (1) the control group injected with deionized water, (2) the glyphosate group injected with 10 mg pure glyphosate/Kg egg mass and (3) the Roundup group injected 10 mg the active ingredient glyphosate in Roundup®/Kg egg. The results of the study revealed a reduction in hatchability in chicks treated with Roundup®. Moreover, change of Lipid concentration in serum and the liver-treated groups. Additionally, increased liver function enzymes and increased oxidative stress in the glyphosate and Roundup® groups. Furthermore, liver tissues showed histological changes and several lipid deposits in glyphosate-treated groups. Hepatic CYP1A2 and CYP1A4 expressions were significantly increased (p < .05) after glyphosate exposure, and suppression of CYP1C1 mRNA expression was significant (p < .05) after Roundup® exposure. The pro-inflammatory cytokines genes IFN-γ and IL-1ß expression were significantly increased (p < .05) after Roundup® exposure. In addition, there were significant differences in the levels of expression genes which are related to lipid synthesis or catabolism in the liver. In conclusion, in ovo glyphosate exposure caused disruption of biotransformation, pro-inflammatory and lipid metabolism in chicks.

Primary hyperparathyroidism associated with colorectal cancer: case report.

The association between colorectal cancer and primary hyperparathyroidism has been reported as case reports in the literature. There are few data regarding the molecular explanation of such coexistence. Here we report a case with synchronous pathologies of primary hyperparathyroidism and colorectal cancer. Furthermore, the patient has a positive family history of the same two pathologies in one of his first-degree relatives. We reviewed the literature to clarify and explain the relationship between these two diseases. We aimed to shed light on the coexistence of such conditions and to clarify if there is a relation between them or if it is just a coincidence.

Ganetespib (STA-9090) augments sorafenib efficacy via necroptosis induction in hepatocellular carcinoma: Implications from preclinical data for a novel therapeutic approach.

Sorafenib, a multikinase inhibitor, is a first-line treatment for advanced hepatocellular carcinoma, but its long-term effectiveness is limited by the emergence of resistance mechanisms. One such mechanism is the reduction of microvessel density and intratumoral hypoxia caused by prolonged sorafenib treatment. Our research has demonstrated that HSP90 plays a critical role in conferring resistance to sorafenib in HepG2 cells under hypoxic conditions and N-Nitrosodiethylamine-exposed mice as well. This occurs through the inhibition of necroptosis on the one hand and the stabilization of HIF-1α on the other hand. To augment the effects of sorafenib, we investigated the use of ganetespib, an HSP90 inhibitor. We found that ganetespib activated necroptosis and destabilized HIF-1α under hypoxia, thus enhancing the effectiveness of sorafenib. Additionally, we discovered that LAMP2 aids in the degradation of MLKL, which is the mediator of necroptosis, through the chaperone-mediated autophagy pathway. Interestingly, we observed a significant negative correlation between LAMP2 and MLKL. These effects resulted in a reduction in the number of surface nodules and liver index, indicating a regression in tumor production rates in mice with HCC. Furthermore, AFP levels decreased. Combining ganetespib with sorafenib showed a synergistic cytotoxic effect and resulted in the accumulation of p62 and inhibition of macroautophagy. These findings suggest that the combined therapy of ganetespib and sorafenib may offer a promising approach for the treatment of hepatocellular carcinoma by activating necroptosis, inhibiting macroautophagy, and exhibiting a potential antiangiogenic effect. Overall, continued research is critical to establish the full therapeutic potential of this combination therapy.

Comparison of Mandibular Volume and Linear Measurements in Patients with Mandibular Asymmetry.

In patients with mandibular asymmetry, the volume of the mandible divided by the mandibular median plane is significantly larger on the non-deviated (N-Dev) side than on the deviated (Dev) side. However, it has been reported that there is no significant difference between the volumes of the N-Dev and Dev sides when the mandibular ramus and body are divided. The purpose of this study was to investigate which region is responsible for the volume difference between the N-Dev and Dev sides. Cone Beam Computed Tomography (CBCT) images of patients with mandibular asymmetry were analyzed by measuring the volume, and linear analysis of the mandibular body, ramus, and condyle on the N-Dev and Dev side was performed. In this study, CBCT images of 37 patients (8 Japanese, 16 Korean, and 13 Egyptian) aged ≥ 18 years with mandibular asymmetry (men: 20, women: 17) were used to evaluate mandibular asymmetry. In patients with mandibular asymmetry, the N-Dev side showed significantly larger values than the Dev side for both volume and linear condyle, ramus, and mandibular body measurements. These results do not differ according to sex or ethnicity. Therefore, it is suggested that the N-Dev side of mandibular asymmetry is large without any regional specificity in pathophysiology.

One Anastomosis Gastric Bypass (OAGB) with a 150-cm Biliopancreatic Limb (BPL) Versus a 200-cm BPL, a Systematic Review and Meta-analysis.

This is a systematic review and meta-analysis that assessed the impact of performing OAGB with a 150-cm BPL versus a 200-cm BPL concerning weight loss, comorbidities remission, and adverse nutritional effects. The analysis included studies that compared patients who underwent OAGB with a 150-cm BPL and 200-cm BPL. Eight studies were eligible for this review after searching in the EMBASE, PubMed central database, and Google scholar. The pooled analysis revealed favoring the 200-cm BPL limb length for weight loss, with a highly significant difference in the TWL% (p=0.009). Both groups showed comparable comorbidities remission. Significantly higher ferritin and folate deficiency rates were found in the 200-cm BPL group. Considering a 200-cm BPL when performing OAGB delivers a better weight loss outcome than a 150-cm BPL, which is at the expense of a more severe nutritional deficiency. No significant differences were found regarding the comorbidities' remission.

Prediction model for the compressive strength of green concrete using cement kiln dust and fly ash.

Integrating artificial intelligence and green concrete in the construction industry is a challenge that can help to move towards sustainable construction. Therefore, this research aims to predict the compressive strength of green concrete that includes a ratio of cement kiln dust (CKD) and fly ash (FA), then recommend the optimum sustainable mixture design. The artificial neural network (ANN) and multiple linear regression techniques are used to build prediction models and statistics using MATLAB and IBM SPSS software. The input parameters are based on 156 data points of concrete components and compressive strengths that are collected from the literature. The developed models have been trained, validated, and tested for each technique. TOPSIS method is used to assign the optimum mixture design according to three sustainable criteria: compressive strength, carbon dioxide (CO2) emission, and cost. The results of ANN models showed a better prediction of the compressive strength with regression (R) equal to 0.928 and 0.986. The optimum mixture includes CKD 10-20% and FA 0-30%. Predicting the compressive strength of green concrete is a non-destructive approach that has sustainable returns including preservation of natural resources, reduction of greenhouse gas emissions, cost, time, and waste to landfill as well as saving energy.

Bisphenol A enhances apoptosis, fibrosis, and biochemical fluctuations in the liver of adult male rats with possible regression after recovery.

Bisphenol A (BPA) is an environmental contaminant that might be harmful. Human exposure to BPA can occur during the fetal and postnatal periods and extends throughout life. This study aimed to estimate the effects of oral administration of BPA on rat liver and assess the possibility of recovery after cessation. Adult male albino rats were orally administered with BPA (50 mg/kg body weight) for 8 weeks, and then one group was left to recover for 4 weeks. Histological, immunohistochemical, biochemical, and quantitative real-time polymerase chain reaction assessments were performed. Loss of hepatic architecture, vascular dilatation congestion, and exudation, as well as cellular vacuolation, fat accumulation, and pyknotic nuclei were detected. Furthermore, inflammatory infiltration, localized metaplasia, and excessive collagen deposition in the portal triad were observed. Expression of Bcl-2-associated X protein and transforming growth factor beta 1 was prominent, denoting apoptosis and fibrosis. After the administration of BPA, serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, cholesterol, triglycerides, and low-density lipoproteins were enhanced. Additionally, total protein, albumin, and high-density lipoproteins decreased. After a recovery for 4 weeks, hepatic cellular and vascular pathologies returned to normal, except for some inflammatory infiltration. Regarding biochemical affection, most of the parameters were directed toward normal during recovery. However, most of them were still significantly different from controls. This explored BPA hepatotoxicity from structural and functional aspects, and the possible spontaneous reversibility was confirmed. However, the precise mechanisms underlying hepatotoxicity or recovery need more in-depth investigations.