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There has been a recent change in global attention towards addressing antimicrobial resistance (AMR) as a result of the concerning increase in mortality rates. Nanomaterials have become highly favorable options for a wide range of industrial and biological uses. The objective of this study was to produce aluminum oxide nanoparticles (Al 2 O 3 NPs) using a crude extract from the fungus Aspergillus sp. WAH23, and then analyze the nanoparticles using UV-analysis, electron microscopy (TEM and SEM), and (FT-IR) and X-ray diffraction (XRD). Results revealed that formed nanoparticles are spherical with an average size of 8.5 nm. XRD analysis confirmed the crystalline nature of the synthesized Al 2 O 3 NPs. The Al 2 O 3 nanoparticles exhibited antibacterial properties against a wide range of pathogenic microbes. The antibacterial efficacy of these nanoparticles on the examined bacterial strains was exhibited through their ability to hinder several metabolic processes, including phosphofructokinase (PFK), enolase, and glutamine synthetase. Additionally, the nanoparticles increased the activity of NADH-oxidase, the content of MDA, and the formation of H 2 O 2 . The study also examined the anticancer properties of Al 2 O 3 nanoparticles on various types of cancer cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

There is an urgent need for preventive and therapeutic drugs to effectively treat and prevent viral diseases from resurfacing as they emerge during the COVID-19 pandemic. This study aims to assess the antiviral effects of four natural compounds commonly used in traditional medicine to treat SARS-CoV-2 infection. A cytotoxicity, dose-dependent, and plaque reduction assay was performed on Vero CCL-81 cells to figure out their effects on the cells. Quantification of cytokines was assessed. In silico analysis for the selected compound was also evaluated. Results revealed that the compounds could disrupt the viral replication cycle through direct inhibition of the virus or immune system stimulation. The cytotoxicity assay results revealed that the compounds were well tolerated by the cells, indicating that the compounds were not toxic to the cells. This study evaluated the antioxidant capacities of propolis, curcumin, quercetin, and ginseng using ABTS, FRAP, and CUPRAC assays, revealing that propolis exhibited the highest antioxidant activity of ABTS with 1250.40 ± 17.10 μmol Trolox eq/g, with FRAP values reaching 1200.55 ± 15.90 μmol Fe 2 ⁺ eq/g and CUPRAC values of 1150.80 ± 14.20 μmol Trolox eq/g at 1000 µg/mL, highlighting its potential as a potent natural antioxidant. The results of the plaque reduction assay revealed that the compounds could reduce the size and number of plaques, indicating that the compounds could inhibit the virus replication cycle. Subsequently, using molecular docking to analyze the effect of propolis, curcumin, quercetin, and ginseng as inhibitors, it was unveiled that the four compounds are likely to have the potential to inhibit the protease activity, spike protein S1, and RNA polymerase of SARS-CoV-2 and the virus titer was reduced by 100% after post-infection using propolis as an inhibitor control., Competing Interests: Declarations. Ethics approval consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background and Aim: Recurrent pregnancy loss (RPL), also known as recurrent implantation failure (RIF), is a distressing condition affecting women characterized by two or more consecutive miscarriages or the inability to carry a pregnancy beyond 20 weeks. Immunological factors and genetic variations, particularly in Vit D Binding Protein (VDBP), have gained attention as potential contributors to RPL. This study aimed to provide insight into the immunological, genetic, and metabolic networks underlying RPL, placing a particular emphasis on the interactions between VDBP, HLA-G1, CTLA-4, ENTPD1, and adenosine-fetal-maternal conflict crosstalk., Methods: A retrospective study included 198 women with three or more consecutive spontaneous abortions. Exclusion criteria comprised uterine abnormalities, endocrine disorders, parental chromosomal abnormalities, infectious factors, autoimmune diseases, or connective tissue diseases. Immunological interplay was investigated in 162 female participants, divided into two groups based on their Vit D levels: normal Vit D-RPL and low Vit D-RPL. Various laboratory techniques were employed, including LC/MS/MS for Vit D measurement, ELISA for protein detection, flow cytometry for immune function analysis, and molecular docking for protein-ligand interaction assessment., Results: General characteristics between groups were significant regarding Vit D and glucose levels. Low Vit D levels were associated with decreased NK cell activity and downregulation of HLA-G1 and HLA-G5 proteins, while CTLA-4 revealed upregulation. VDBP was significantly downregulated in the low Vit D group. Our findings highlight the intricate relationship between Vit D status and adenosine metabolism by the downregulation of SGLT1, and NT5E, key components of adenosine metabolism, suggests that Vit D deficiency may disrupt the regulation of adenosine levels, leading to an impaired reproductive outcome. HNF1β, a negative regulator of VDBP, was upregulated, while HNF1α, a positive regulator, was downregulated in low Vit D women after RPL. Molecular docking analysis revealed crucial residues involved in the interaction between Vit D and HNF1β., Conclusion: Collectively, these findings underscore the importance of Vit D in modulating immune function and molecular pathways relevant to pregnancy maintenance, highlighting the need for further research to elucidate the mechanisms and potential therapeutic interventions for improving pregnancy outcomes in individuals with Vit D deficiency and RPL., (© 2024. The Author(s).)

Idiopathic male infertility, a significant health concern, lacks a clear etiology. Cadmium (Cd), a widespread environmental pollutant known to impact male reproductive health negatively, can accumulate in mussels, a common food source in Egypt. This study investigated the link between ecological Cd exposure, oxidative stress, MT1A methylation, and idiopathic male infertility in two regions of Alexandria. Thirty-three infertile men and 33 fertile controls were included. Cd levels were measured in mussels from the study sites and in participants' blood and semen. Biomarkers reflecting Cd exposure and its effects were assessed. Mussel Cd levels exceeded regulatory limits. Infertile men revealed significantly higher blood and semen Cd levels, reduced semen quality, increased oxidative stress, and elevated MT1A methylation compared to controls. MT1A methylation was inversely correlated with sperm count and is the strongest predictor of idiopathic male infertility, demonstrating the lowest p-value and considerable effect size. This study suggests that environmental Cd exposure, potentially through mussel consumption, may contribute to idiopathic male infertility in Egypt by increasing oxidative stress, inducing epigenetic modifications, and impairing semen quality. These findings underscore the need for further research into the mechanisms underlying Cd-induced male infertility and the development of preventative strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Aim: Metabolic dysfunction-associated steatotic liver disease (MASLD) formerly known as non-alcoholic fatty liver disease (NAFLD) is the most common liver condition globally. The FIB-4 test is used to detect fibrosis in fatty liver disease but has limited accuracy in predicting liver stiffness, resulting in high rates of false positives and negatives. The new BAST scoring system, incorporating waist circumference, AST, and BMI, has been developed to assess the presence of fibrosis in NAFLD patients. This study compares the effectiveness of BAST and FIB-4 in predicting liver fibrosis in MASLD patients., Patients and Methods: The study included 140 non-diabetic MASLD patients who underwent transient elastography measurement. BAST score and FIB-4 were calculated for each patient. Patients were grouped based on fibrosis severity; F1, F2, and F3-F4. The sensitivity and specificity of the BAST score and FIB-4 were assessed using receiver operating characteristic curves., Results: The BAST score increased significantly with fibrosis progression from F1 to F3-F4. In differentiating advanced fibrosis (F2-F3) from mild/moderate fibrosis (F1-F2), the BAST score at cutoff ≤ - 0.451 showed better diagnostic performance with 90.70% sensitivity, 74.07% specificity, 84.8% PPV and 83.3% NPV compared to FIB-4 that had 60.47% sensitivity, 50.0% specificity, 65.8% PPV and 44.3% NPV. Similarly, for differentiating between F1 and F2 fibrosis, the BAST score at cutoff ≤ - 1.11 outperformed FIB-4, with 80.23% sensitivity, 79.49% specificity, 89.6% PPV and 64.6% NPV, while FIB-4 had 59.30% sensitivity, 51.28% specificity, 72.9% PPV and 36% NPV., Conclusions: The BAST score is a better predictor of liver fibrosis in MASLD compared to FIB-4, especially in cases of advanced fibrosis or cirrhosis., (© 2024. The Author(s).)

Background: Type 2 Diabetes Mellitus (T2DM) is a global health concern associated with numerous complications. Aerobic exercise is recognized as a crucial non-pharmacological intervention for T2DM management, but its specific effects on key health parameters warrant further investigation., Objective: This study aimed to evaluate the impact of a structured 8-week aerobic exercise program on fasting blood glucose (FBG), glycated haemoglobin (HbA1c), body mass index (BMI), blood pressure (BP), and resting heart rate (RHR) in individuals with T2DM., Methods: A prospective study was conducted with 100 participants diagnosed with T2DM. The intervention group (n = 50) underwent a supervised aerobic exercise program for eight weeks, while the control group (n = 50) received no structured exercise intervention. Pre- and post-intervention assessments were conducted to measure FBG, HbA1c, BMI, BP, RHR, and VO₂ max were taken., Results: The aerobic group exhibited a significant reduction in FBG, declining from 141 to 132 mg/dl. Correspondingly, HbA1c decreased from 7.93 to 7.15%. Additionally, the aerobic group demonstrated a notable decrease in RHR from 72 to 66 bpm, indicating improved cardiovascular fitness. Concurrently, VO2 max increased from 22 to 26 mL/kg/min, further supporting the enhancement of cardiorespiratory capacity. Trends toward improvement were also observed in SBP and DBP. Correlation analysis revealed significant relationships between various health parameters, highlighting the interconnectedness of these variables in T2DM management., Conclusions: This study provides robust evidence supporting the benefits of aerobic exercise in individuals with T2DM. The improvements in glycemic control, blood pressure, and cardiorespiratory fitness underscore the importance of incorporating structured exercise programs into diabetes management protocols. The results emphasize the importance of incorporating regular physical activity into diabetes management strategies to optimize health outcomes and reduce the risk of complications., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Recent advances in nanotechnology have offered novel ways to combat cancer. By utilizing the reducing capabilities of Lactobacillus acidophilus, silver nanoparticles (AgNPs) are synthesized. The anti-cancer properties of AgNPs have been demonstrated in previous studies against several cancer cell lines; it has been hypothesized that these compounds might inhibit AMPK/mTOR signalling and BCL-2 expression. Consequently, the current research used both in vitro and in silico approaches to study whether Lactobacillus acidophilus AgNPs could inhibit cell proliferation autophagy and promote apoptosis in HepG2 cells. The isolated strain was identified as Lactobacillus acidophilus strain RBIM based on 16 s rRNA gene analysis. Based on our research findings, it has been observed that this particular strain can generate increased quantities of AgNPs when subjected to optimal growing conditions. The presence of silanols, carboxylates, phosphonates, and siloxanes on the surface of AgNPs was confirmed using FTIR analysis. AgNPs were configured using UV-visible spectroscopy at 425 nm. In contrast, it was observed that apoptotic cells exhibited orange-coloured bodies due to cellular shrinkage and blebbing initiated by AgNP treatment, compared to non-apoptotic cells. It is worth mentioning that AgNPs exhibited remarkable selectivity in inducing cell death, specifically in HepG2 cells, unlike normal WI-38 cells. The half-maximum inhibitory concentration (IC 50 ) values for HepG2 and WI-38 cells were 4.217 µg/ml and 154.1 µg/ml, respectively. AgNPs induce an upregulation in the synthesis of inflammation-associated cytokines, including (TNF-α and IL-33), within HepG2 cells. AgNPs co-treatment led to higher glutathione levels and activating pro-autophagic genes such as AMPK.Additionally, it resulted in the suppression of mTOR, MMP-9, BCL-2, and α-SMA gene expression. The docking experiments suggest that the binding of AgNPs to the active site of the AMPK enzyme leads to inhibiting its activity. The inhibition of AMPK ultimately results in the suppression of the mechanistic mTOR and triggers apoptosis in HepG2 cells. In conclusion, the results of our study indicate that the utilization of AgNPs may represent a viable strategy for the eradication of liver cancerous cells through the activation of apoptosis and the enhancement of immune system reactions., (© 2024. The Author(s).)

Background: The neutrophil percentage-to-albumin ratio (NPAR) is a novel measure of systemic inflammation and infection. Low albumin levels increase the risk of infection, while high neutrophil counts indicate the presence of infection. Spontaneous bacterial peritonitis (SBP) is a serious infection in cirrhotic ascites, and the potential of NPAR in diagnosing SBP is not yet established., Objective: The objective of this study is to determine the diagnostic value of NPAR in identifying SBP., Patients: This prospective multicenter study included 465 patients diagnosed with cirrhotic ascites and SBP according to international guidelines. Demographic, clinical, and laboratory data were collected. The sensitivity and specificity of NPAR values for diagnosing SBP were assessed using the receiver operating characteristic curve., Results: For SBP diagnosis in the total cohort, NPAR of > 17 had a sensitivity of 85.71%, specificity of 66.67%, and 95% CI (42.1-99.6). In culture-positive SBP, the NPAR at a cut-off > 5.2 had a sensitivity of 85.71%, specificity of 83.33%, and 95% CI (0.709 to 0.979), while in culture-negative SBP, the NPAR at a cut-off > 2.1 had a sensitivity of 92.86%, specificity of 33.33% and CI (0.367 to 0.764). The multivariate analysis revealed that albumin (OR = 2.78, [1.11;3.98], INR (OR = 0.198, [0.066;0.596], creatinine (OR = 0.292, [0.1; 0.81], CRP (OR = 3.18, [1.239;4.52] total leukocytic count (TLC) (OR = 1.97, [1.878; 2.07], platelets (OR = 2.09, [0.99; 2.31] and neutrophil (OR = 3.43, [1.04;3.89] were significantly associated with higher prediction rates for culture positive SBP., Conclusions: NPAR could be a new, affordable, noninvasive test for diagnosing SBP., (© 2024. The Author(s).)

Background: Cytokines play a crucial role in regulating the function of the immune system by controlling the production, differentiation, and activity of immune cells. Occult hepatitis C virus (OHCV) infection can lead to liver damage, including cirrhosis and hepatocellular carcinoma. This study investigates the immunopathogenic impact of the cytokines IL-17 and IL-22 in OHCV infection compared to chronic hepatitis C (CHC) infection., Methods: We studied three groups of patients: 35 with OHCV, 100 untreated patients with CHC, and 30 healthy control subjects. All subjects underwent physical examination and biochemical testing. We used the sandwich enzyme-linked immunosorbent assay method to measure serum IL-17 and IL-22 levels in all groups., Results: Compared to the occult and control groups, the CHC group had significantly higher serum IL-17 levels (p < 0.001). The occult group also had higher serum IL-17 levels compared to the control group (p < 0.0001). There were no significant differences in IL-22 levels across the research groups. In the OHCV group, individuals with moderate inflammation (A2-A3) had significantly higher serum IL-17 levels than those with minimal inflammation (A0-A1), while in the CHC group, this difference was not statistically significant (p = 0.601). Neither the occult nor the CHC groups showed a correlation between serum IL-22 and inflammatory activity. There was no significant correlation between the levels of IL-17 or IL-22 and the stage of fibrosis/cirrhosis in either group. ROC curves were calculated for serum IL-17 and IL-22 levels and occult HCV infection, with cut-off values set at ≤ 32.1 pg/ml and < 14.3 pg/ml for IL-17 and IL-22, respectively. The AUROC (95%CI) was significantly higher for IL-17 than IL-22 (0.829 (0.732-0.902) vs. 0.504 (0.393-0.614), p < 0.001), suggesting that IL-17 has a stronger correlation with infection risk than IL-22., Conclusion: This study suggests that IL-17 may be involved in the immunopathogenesis of OHCV infection, especially in patients with moderate inflammation., (© 2024. The Author(s).)

Ginger (Gin) has numerous therapeutic properties. One of Gin's most potent components is 6-gingerol, a naturally occurring phenol. This study aimed to investigate the therapeutic impact of gingerol and/or sorafenib on the ATG4/CASP3 and COIIV/COX-2/NF-B Expression as a potential therapy for DAB-induced HCC. Gin was administered to HCC mice induced by p-Dimethylaminoazobenzene (DAB) alone or combined with sorafenib (Sor). Superoxide dismutase (SOD), catalase (CAT), and oxidative stress malondialdehyde (MDA), as well as biochemical markers including AST, ALT, ALP, Albumin, and Bilirubin, were examined. The expression of oncogenes (COIIV, COX-2, NF-κB, and survivin) and tumor suppressor genes (ATG4 and CASP3) was evaluated using qPCR. According to the results, the levels of MDA have been markedly decreased, while SOD and CAT have been increased. Further, the expression levels of tumor suppressor genes were upregulated, whereas the expression levels of oncogene genes were downregulated. Furthermore, in a dose-dependent manner, gingerol has shown the potential to alleviate hepatic portal vein (PV) dilatation and could offer a reliable therapy for HCC. This suggests combining the two compounds may be more effective than alone and that Gin could be a promising therapeutic option for HCC. The binding of Gin and Sor to the active sites of the target genes prevents them from functioning normally, which in turn stops the pathways from carrying out their oncogenic functions. Additionally, COX-2 inhibition reduces the production of certain pro-inflammatory compounds, which further averts oncogenesis. Conclusively, this study indicated that Gin has cytoprotective properties and anti-cancer activity that may be related to controlling oxidative stress. This effect may be achieved by suppressing the COIIV/COX-2/NF-κB pathway and upregulating the ATG4 /CASP3 pathways., (© 2024. The Author(s).)

A wide variety of health benefits have been demonstrated by medicinal plants, including potent antiviral properties. Additionally, many herbal remedies are known to reduce inflammation and boost immunity, making them an effective preventive measure against viral infections. The study aims to evaluate the perception of medicinal herbs and healthy foods during the pandemic period among Saudi patients. Furthermore, the study seeks to understand how people view medicinal herbs and healthy foods as a means of mitigating the effects of the pandemic and how that perception varies across different demographics. It will also assess the availability of these options in the country and how they have been utilized by the population. A cross-sectional online study was conducted among COVID-19-infected Saudi population at the University of Tabuk, Saudi Arabia. The perception of the use of medicinal herbs and the effect of healthy foods on the treatment or reduction of symptoms of COVID-19 was evaluated. The efficacy of 23 herbal products was evaluated. A total of 909 participants with COVID-19 infection were surveyed; 86.14% were women, 93.73% were between the ages of 18-60, 51.05% were unemployed, 57.43% had a bachelor's degree, and 90.64% were non-smokers. Study participants used medicinal herbs, slime drinks, and medicinal herb tea to reduce coronavirus infection risk by 67.11, 43.56, and 7.18%, respectively. Gender, education, consuming healthy food, and drinking medicinal herbs displayed significant variation among the studied participants (p < 0.001). The study revealed a prevalence of ginger (62.9%), lemon (51.1%), mint (46.8%), honey (45.7%), and anise (43.0%) as commonly used medicinal herb products. To conclude, the survey found a link between gender, education, consuming healthy foods, and drinking medicinal herbs to reduce infection symptoms among Saudi Arabians. Accordingly, lifestyle choices can have a positive impact on health, even in the face of a challenging environment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The glutamine synthetase (GS) facilitates cancer cell growth by catalyzing de novo glutamine synthesis. This enzyme removes ammonia waste from the liver following the urea cycle. Since cancer development is associated with dysregulated urea cycles, there has been no investigation of GS's role in ammonia clearance. Here, we demonstrate that, although GS expression is increased in the setting of β-catenin oncogenic activation, it is insufficient to clear the ammonia waste burden due to the dysregulated urea cycle and may thus be unable to prevent cancer formation. In vivo study, a total of 165 male Swiss albino mice allocated in 11 groups were used, and liver cancer was induced by p-DAB. The activity of GS was evaluated along with the relative expression of mTOR, β-catenin, MMP-14, and GS genes in liver samples and HepG2 cells using qRT-PCR. Moreover, the cytotoxicity of the NH3 scavenger phenyl acetate (PA) and/or GS-inhibitor L-methionine sulfoximine (MSO) and the migratory potential of cells was assessed by MTT and wound healing assays, respectively. The Swiss target prediction algorithm was used to screen the mentioned compounds for probable targets. The treatment of the HepG2 cell line with PA plus MSO demonstrated strong cytotoxicity. The post-scratch remaining wound area (%) in the untreated HepG2 cells was 2.0%. In contrast, the remaining wound area (%) in the cells treated with PA, MSO, and PA + MSO for 48 h was 61.1, 55.8, and 78.5%, respectively. The combination of the two drugs had the greatest effect, resulting in the greatest decrease in the GS activity, β-catenin, and mTOR expression. MSO and PA are both capable of suppressing mTOR, a key player in the development of HCC, and MMP-14, a key player in the development of HCC. PA inhibited the MMP-14 enzyme more effectively than MSO, implying that PA might be a better way to target HCC as it inhibited MMP-14 more effectively than MSO. A large number of abnormal hepatocytes (5%) were found to be present in the HCC mice compared to mice in the control group as determined by the histopathological lesions scores. In contrast, PA, MSO, and PA + MSO showed a significant reduction in the hepatic lesions score either when protecting the liver or when treating the liver. The molecular docking study indicated that PA and MSO form a three-dimensional structure with NF-κB and COX-II, blocking their ability to promote cancer and cause gene mutations. PA and MSO could be used to manipulate GS activities to modulate ammonia levels, thus providing a potential treatment for ammonia homeostasis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hepatocellular carcinoma (HCC) is commonly associated with disturbances in glucose metabolism and enhanced glycolysis. However, a controversial role for gluconeogenesis was reported to be tumor-promoting and tumor-suppressive. We investigated novel anti-HCC treatments through either the simultaneous inhibition of glycolysis and gluconeogenesis by "phloretin" and "sodium meta-arsenite", respectively (Combination 1); or the concurrent inhibition of glycolysis and induction of gluconeogenesis by phloretin and dexamethasone, respectively, (combination 2). A total of 110 Swiss albino mice were divided into eleven groups, HCC was induced by N, N-dimethyl-4-aminoazobenzene. We have measured the expression of the glucose transporter 2 (GLUT2), Phosphoenolpyruvate carboxykinases (PEPCK), Caspase-3, Beclin 1, Cyclin D1, and cytokeratin 18 genes; blood glucose and ATP levels; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Furthermore, in silico molecular docking was performed to investigate the potential drug-receptor interactions. Histologically, the phloretin-based combinations resulted in a significant regression of malignant tissue compared to various treatments. GLUT2 and PEPCK mRNA analysis indicated successful off/on modulation of glycolysis and gluconeogenesis. Docking confirmed the potent binding between phloretin, sodium meta-arsenite, and dexamethasone with GLUT2, PEPCK, and Retinoid X Receptor Alpha, respectively. Molecularly, Combination 2 resulted in the highest reduction in cyclin D1, cytokeratin 18, and Beclin 1 expression contemporaneously with the upregulation in Caspase-3 levels. Biochemically, both combinations caused a significant reduction in ATP levels, ALT, and AST activity compared to the other groups. In conclusion, we propose two novel phloretin-based combinations that can be used in treating HCC through the regulation of glucose metabolism and ATP production., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cancer cells can become resistant to existing treatments over time, so it is important to develop new treatments that target different pathways to stay ahead of this resistance. Many cancer treatments have severe side effects that can be debilitating and even life-threatening. Developing drugs that can effectively treat cancer while minimizing the risks of these side effects is essential for improving the quality of life of cancer patients. The study was designed to explore whether the combination of dicinnamoyl-L-tartaric (CLT) and sorafenib ((SOR), an anti-cancer drug)) could be used to treat hepatocellular carcinoma (HCC) in the animal model and to assess whether this combination would lead to changes in certain biomarkers associated with the tumour. In this study, 120 male mice were divided into 8 groups of 15 mice each. A number of biochemical parameters were measured, including liver functions, oxidative stress (malondialdehyde, (MDA); nitric oxide (NO)), and antioxidative activity (superoxide dismutase (SOD), and glutathione peroxidase (GPx)). Furthermore, the hepatic expressions of Bax, Beclin1, TNF-α, IL1β, and BCl-2 genes were evaluated by qRT-PCR. The combination of SOR and CLT was found to reduce the levels of liver enzymes, such as AST, ALT, ALP, and GGT, and reduce the pathological changes caused by DAB and PB. The upregulation of TNF-α, IL1β, and Bcl-2 genes suggests that the CLT was able to initiate an inflammatory response to combat the tumor, while the downregulation of the Bax and Beclin1 genes indicates that the CLT was able to reduce the risk of apoptosis in the liver. Furthermore, the combination therapy led to increased expression of cytokines, resulting in an enhanced anti-tumor effect., (© 2023. The Author(s).)

Hepatocellular carcinoma (HCC) is a serious and potentially fatal form of cancer associated with liver damage. New anticancer drugs are increasingly needed due to the increasing number of cancer cases every year. In this study, diarylheptanoids (DAH) from Alpinia officinarum were examined for their antitumor activity against DAB-induced HCC in mice, as well as their ability to reduce liver damage. Assays for cytotoxicity were conducted using MTT. The DAB-induced HCC Swiss albino male mice were given DAH and sorafenib (SOR) either as single treatments or in combination, and the effects on tumour development and progression were monitored. Malondialdehyde (MDA) and total superoxide dismutase (T-SOD) were evaluated along with biomarkers of liver enzymes (AST, ALT, and GGT). The apoptosis-related gene (CASP8), the apoptosis-related gene (p53), the anti-inflammatory genes (IL-6), the migration-related gene matrix metalloprotease-9 (MMP9), and the angiogenesis-related gene vascular endothelial growth factor (VEGF) were assessed using qRT-PCR in the hepatic tissue. As a final step, DAH and SOR were docked with CASP8 and MMP9 via molecular docking to propose potential mechanisms of action. Our results revealed that the combination of DAH and SOR has a potent inhibitory effect on the growth and viability of the HepG2 cell line. The outcomes demonstrated that DAH and SOR-treated HCC-bearing mice displayed a reduction in the tumour burden and liver damage as demonstrated by (1) parameters of repaired liver function; (2) low levels of hepatic MDA; (3) elevated levels of hepatic T-SOD; (4) p53, IL-6, CASP8, MMP9, and VEGF downregulation; and (5) enhanced hepatic structure. The best results were revealed in mice that were co-treated with DAH (given orally) and SOR (given intraperitoneally). The docking study also proposed that both DAH and SOR could inhibit CASP8 and MMP9's oncogenic activities and had a high affinity for these enzymes. In conclusion, according to study findings, DAH enhances SOR antiproliferative and cytotoxic effects and identifies their molecular targets. Furthermore, the results revealed that DAH was able to boost the anticancer effects of the drug SOR and reduce liver damage caused by HCC in mice. This suggests that DAH could be a potential therapeutic agent against liver cancer., (© 2023. The Author(s).)

Background: Sorafenib (Sor) is the only approved multikinase inhibitor indicated for the treatment of HCC. Previous studies have shown that amygdalin (Amy) possesses anticancer activities against several cancer cell lines; we suggested that these compounds might disrupt AMPK/mTOR and BCL-2. Therefore, the current study used integrated in vitro and in silico approaches to figure out Amy and Sor's possible synergistic activity in targeting AMPK/mTOR and BCL-2 for anti-angiogenesis and apoptosis cell death in HepG2 cells., Results: Notably, Amy demonstrated exceptional cytotoxic selectivity against HepG2 cells in comparison to normal WI-38 cells (IC 50  = 5.21 mg/ml; 141.25 mg/ml), respectively. In contrast, WI-38 cells were far more sensitive to the toxicity of Sor. A substantial synergistic interaction between Amy and Sor was observed (CI 50  = 0.56), which was connected to cell cycle arrest at the S and G2/M stages and increased apoptosis and potential necroptosis. Amy and Sor cotreatment resulted in the highest glutathione levels and induction of pro-autophagic genes AMPK, HGMB1, ATG5, Beclin 1, and LC3, suppressed the mTOR and BCL2 anti-apoptotic gene. Finally, the docking studies proposed that Amy binds to the active site of the AMPK enzyme, thus inhibiting its activity. This inhibition of AMPK ultimately leads to inhibition of mTOR and thus induces apoptosis in the HepG2 cells., Conclusion: Although more in vivo research using animal models is needed to confirm the findings, our findings contribute to the evidence supporting Amy's potential anticancer effectiveness as an alternative therapeutic option for HCC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background and Aim: There is lack of 30-day hospital readmission prediction score in patients with liver cirrhosis and SBP. The aim of this study is to recognize factors capable of predicting 30-day readmission and to develop a readmission risk score in patients with SBP., Methods: This study prospectively examined the 30-day hospital readmission for patients previously discharged with a diagnosis of SBP. Based on index hospitalization variables, a multivariable logistic regression model was implemented to recognize predictors of patient hospital readmission within 30 days. Consequently, Mousa readmission risk score was established to predict 30-day hospital readmission., Results: Of 475 patients hospitalized with SBP, 400 patients were included in this study. The 30-day readmission rate was 26.5%, with 16.03% of patients readmitted with SBP. Age ≥ 60, MELD > 15, serum bilirubin > 1.5 mg/dL, creatinine > 1.2 mg/dL, INR > 1.4, albumin < 2.5 g/dL, platelets count ≤ 74 (10 3 /dL) were found to be independent predictors of 30-day readmission. Incorporating these predictors, Mousa readmission score was established to predict 30-day patient readmissions. ROC curve analysis demonstrated that at a cutoff value ≥ 4, Mousa score had optimum discriminative power for predicting the readmission in SBP with sensitivity 90.6% and specificity 92.9%. However, at cutoff value ≥ 6 the sensitivity and specificity were 77.4% and 99.7%, respectively, while a cutoff value ≥ 2 had sensitivity of 99.1% and specificity of 31.6%., Conclusions: The 30-day readmission rate of SBP was 25.6%. With the suggested simple risk assessment Mousa score, patients at high risk for early readmission can be easily identified so as to possibly prevent poorer outcomes., (© 2023. The Author(s).)

Environmental contamination by phenol has been reported in both aquatic and atmospheric environments. This study aimed to separate and purify the peroxidase enzyme from bacteria that degrade phenol from wastewater sources. An enrichment culture of MSM was used to screen 25 bacterial isolates from different water samples for peroxidase production, six of the isolates exhibited high levels of peroxidase enzyme activity. Qualitative analysis of peroxidase revealed that isolate No. 4 had the highest halo zones (Poly-R478: 14.79 ± 0.78 mm, Azure B: 8.81 ± 0.61 mm). The promising isolate was identified as Bacillus aryabhattai B8W22 by 16S rRNA gene sequencing with accession number OP458197. As carbon and nitrogen sources, mannitol and sodium nitrate were utilized to achieve maximum peroxidase production. A 30-h incubation period was used with pH 6.0, 30 °C, mannitol, and sodium nitrate, respectively, for maximal production of peroxidase. Purified peroxidase enzyme showed 0.012 U/mg specific activity, and SDS-PAGE analysis indicated a molecular weight of 66 kDa. The purified enzyme exhibits maximum activity and thermal stability at pH values of 4.0 and 8.0, respectively, with maximum activity at 30 °C and complete thermal stability at 40 °C. In the purified enzyme, the Km value was 6.942 mg/ml and the Vmax value was 4.132 mol/ml/hr, respectively. The results demonstrated that Bacillus aryabhattai B8W22 has promising potential for degrading phenols from various phenol-polluted wastewater sources., (© 2023. The Author(s).)

Aniseeds ( Pimpinella anisum ) have gained increasing attention for their nutritional and health benefits. Aniseed extracts are known to contain a range of compounds, including flavonoids, terpenes, and essential oils. These compounds have antimicrobial properties, meaning they can help inhibit the growth of nasty bacteria and other microbes. The purpose of this study was to determine if aniseed extracts have potential antioxidant, phytochemical, and antimicrobial properties against multidrug-resistant (MDR) bacteria. A disc diffusion test was conducted in vitro to test the aniseed methanolic extract's antibacterial activity. The MIC, MBC, and inhibition zone diameters measure the minimum inhibitory concentration, minimum bactericidal concentration, and size of the zone developed when the extract is placed on a bacterial culture, respectively. HPLC and GC/MS are analytical techniques used for identifying the phenolics and chemical constituents in the extract. DPPH, ABTS, and iron-reducing power assays were performed to evaluate the total antioxidant capacity of the extract. Using HPLC, oxygenated monoterpenes represented the majority of the aniseed content, mainly estragole, cis -anethole, and trans -anethole at 4422.39, 3150.11, and 2312.11 (g/g), respectively. All of the examined bacteria are very sensitive to aniseed's antibacterial effects. It is thought that aniseed's antibacterial activity could be attributed to the presence of phenolic compounds which include catechins, methyl gallates, caffeic acid, and syringic acids. According to the GC analysis, several flavonoids were detected, including catechin, isochiapin, and trans -ferulic acid, as well as quercitin rhamnose, kaempferol- O -rutinoside, gibberellic acid, and hexadecadienoic acid. Upon quantification of the most abundant estragole, we found that estragole recovery was sufficient for proving its antimicrobial activity against MDR bacteria. Utilizing three methods, the extract demonstrated strong antioxidant activity. Aniseed extract clearly inhibited MDR bacterial isolates, indicating its potential use as an anti-virulence strategy. It is assumed that polyphenolic acids and flavonoids are responsible for this activity. Trans -anethole and estragole were aniseed chemotypes. Aniseed extracts showed higher antioxidant activity than vitamin C. Future investigations into the compatibility and synergism of aniseed phenolic compounds with commercial antibacterial treatments may also show them to be promising options.

Background: Traditional herbal medicine has been used for centuries to cure many pathological disorders, including cancer. Thymoquinone (TQ) and piperine (PIP) are major bioactive constituents of the black seed (Nigella sativa) and black pepper (Piper nigrum), respectively. The current study aimed to explore the potential chemo-modulatory effects, mechanisms of action, molecular targets, and binding interactions after TQ and PIP treatments and their combination with sorafenib (SOR) against human triple-negative breast cancer (MDA-MB-231) and liver cancer (HepG2) cells., Methods: We determined drug cytotoxicity by MTT assay, cell cycle, and death mechanism by flow cytometry. Besides, the potential effect of TQ, PIP, and SOR treatment on genome methylation and acetylation by determination of DNA methyltransferase (DNMT3B), histone deacetylase (HDAC3) and miRNA-29c expression levels. Finally, a molecular docking study was performed to propose potential mechanisms of action and binding affinity of TQ, PIP, and SOR with DNMT3B and HDAC3., Results: Collectively, our data show that combinations of TQ and/or PIP with SOR have significantly enhanced the SOR anti-proliferative and cytotoxic effects depending on the dose and cell line by enhancing G2/M phase arrest, inducing apoptosis, downregulation of DNMT3B and HDAC3 expression and upregulation of the tumor suppressor, miRNA-29c. Finally, the molecular docking study has identified strong interactions between SOR, PIP, and TQ with DNMT3B and HDAC3, inhibiting their normal oncogenic activities and leading to growth arrest and cell death., Conclusion: This study reported TQ and PIP as enhancers of the antiproliferative and cytotoxic effects of SOR and addressed the mechanisms, and identified molecular targets involved in their action., (© 2023. The Author(s).)

The burden of cancer diseases is increasing every year, therefore, the demands to figure out novel drugs that can retain antitumor properties have been raised. This study aimed to investigate the anti-tumor properties of amygdalin (Amy) against Ehrlich ascites carcinoma (EAC) bearing mice and its protective properties against liver damage. Amy and the standard anticancer drug Sorafenib (Sor) were given alone or in combination to Swiss albino female mice that had been injected with EAC cells. Biochemical parameters of liver function (AST, ALT, GGT, total protein, albumin), tumor volume, oxidative stress [malondialdehyde, (MDA)] and antioxidative [superoxide dismutase (SOD), and reduced glutathione (GSH)] markers were measured. The hepatic expression of the antioxidant-related gene [nuclear factor erythroid-2-related factor 2 (Nrf2)], the migration-related gene [matrix metalloprotease 9 (MMP9)], and the angiogenesis-related gene [vascular endothelial growth factor (VEGF)] were evaluated by qPCR. The results revealed that EAC-bearing mice treated with Amy and/or Sor showed a decrease in the tumor burden and hepatic damage as evidenced by (1) decreased tumor volume, number of viable tumor cells; (2) increased number of dead tumor cells; (3) restored the liver function parameters; (4) reduced hepatic MDA levels; (5) enhanced hepatic GSH and SOD levels; (6) upregulated expression of Nrf2; (7) downregulated expression of MMP9 and VEGF, and (8) improved hepatic structure. Among all treatments, mice co-treated with Amy (orally) and Sor (intraperitoneally) showed the best effect. With these results, we concluded that the Amy improved the antitumor effect of Sor and had a protective role on liver damage induced by EAC in mice., (© 2022. The Author(s).)