The sub-acute toxicity of kavalactone in rats: a study of the effect of oral doses and the mechanism of toxicity in combination with ethanol.

Kava is a herbal supplement and beverage made from the Piper methysticum plant, which is known for its recreational use as a mood enhancer, relaxation, as well as pain relief for centuries. Kava is widely used among alcoholics, but it is dangerous and potentially fatal. The objectives of this study were to examine the sub-acute toxicity effects of different doses of 70% kavalactone (KL) in rats by oral application, as well as to elucidate the mechanisms of toxicity alone and in combination with ethanol (EtOH). The most common side effects observed were abnormal breathing, ataxia, lethargy, loss of appetite, indigestion, and loss of coordination, especially in the 800 mg/kg bw, po bodyweight dosage of kava treatment group alone, and in combination with EtOH. In the sub-acute study, there were dose-related decreases in body weight, feed intake, and water consumption rates. Gross and histopathological findings revealed that the liver was abnormal in color, size, consistency, and the weight significantly increased at a dose of 800 mg/kg bw, po, with KL alone and a greater increase in combination with EtOH. Hepatocellular hypertrophy (HP) and necrosis with Kupffer cells hyperplasia were observed in the periacinar zone of all rats dosed with KL (800 mg/kg bw, po) alone, and extensive changes were observed in combination with EtOH. The periportal (Z1) and mid-zonal (Z2) areas of hepatocytes were less affected as compared to the periacinar zone. These results demonstrate that EtOH exacerbated the sedative and hypnotic activity of KL, and markedly increased toxicity. The histopathological results supported the clinical and biochemical findings and the severity of hepatic damage in a dose-dependent manner.

Effects of nitric oxide modulators and antioxidants on endocrine and cellular markers of acute stress in rats.

The effects of nitric oxide modulators (NO-modulators) and antioxidants on acute (RSx1) restraint stress induced endocrine, cellular and oxidative/nitrosative stress markers was studied in Wistar rats. The results of our study revealed that exposure to RS(x1) enhanced malondialdehyde (MDA), heat shock protein (HSP-70), corticosterone, nuclear factor kappa B (NF-κB) levels and suppressed glutathione (GSH), superoxide dismutase (SOD) and total nitrites and nitrates (NOx) levels. NO precursor and NO synthase inhibitors were found to differentially modulate stress mechanisms, by altering NF-κB, HSP-70 and corticosterone levels. l-Ascorbic acid significantly suppressed acute stress induced elevation of NF-κB and HSP-70 levels depicting protective effects, as also evidenced by reversal of elevated plasma corticosterone levels. Therefore, modulation of oxidative and nitrosative pathways, offers an approach in modulating stress induced changes associated with various disorders.

p-Trifluoromethyl- and p-pentafluorothio-substituted curcuminoids of the 2,6-di[(E)-benzylidene)]cycloalkanone type: Syntheses and activities against Leishmania major and Toxoplasma gondii parasites.

A series of the title curcuminoids with structural variance in the heteroatom of the cycloalkanone and the p-substituents of the phenyl rings were tested for their activities against Leishmania major and Toxoplasma gondii parasites. The majority of them showed high activities against both parasite forms with EC50 values in the sub-micromolar concentration range. Bis(p-pentafluorothio)-substituted 3,5-di[(E)-benzylidene]piperidin-4-one 1b was not just noticeable antiparasitic, but also exhibited a considerable selectivity for L. major promastigotes over normal Vero cells. While derivatives differing only in the p-phenyl substituents being CF3 or SF5 showed similar antiparasitic activities, the cyclic ketone hub was more decisive both for the anti-parasitic activities and the selectivities for the parasites vs. normal cells. QSAR calculations confirmed the observed structure-activity relations and suggested structural variations for a further improvement of the antiparasitic activity. Docking studies based on DFT calculations revealed L. major pteridine reductase 1 as a likely molecular target protein of the title compounds.

Long-term exposure to triclosan increases migration and invasion of human breast epithelial cells in vitro.

Extensive use of triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) as an antimicrobial agent in household and personal care products has resulted in global exposure of the human population. Its presence in human tissues, including milk, and its oestrogen-disrupting properties raise concerns for an involvement in breast cancer. Because metastatic tumour spread is the main cause of breast cancer mortality, we have investigated the effects of triclosan on cell migration and invasion using three human breast epithelial cell lines and using concentrations comparable with those in human tissues. Long-term exposure to 10-7 M of triclosan resulted in increased migration and invasion as measured by xCELLigence technology for all three cell lines, for the immortalized but nontransformed MCF-10F breast epithelial cells (after 28 weeks), the oestrogen-responsive MCF-7 breast cancer cells (after 17 weeks) and the oestrogen-unresponsive MDA-MB-231 breast cancer cells (after 20 weeks). The effects were therefore not limited to cancerous cells or to oestrogen-responsive cells. This was paralleled in the MCF-10F and MCF-7 (but not MDA-MB-231) cells by a reduction in levels of E-cadherin mRNA as measured by reverse transcription-polymerase chain reaction (RT-PCR) and of E-cadherin protein as measured by western immunoblotting, suggesting a mechanism involving epithelial-to-mesenchymal transition. This adds triclosan to the increasing list of ingredients of personal care products that can not only enter human breast tissue and increase cell proliferation but also influence cell motility. If mixtures of components in household and personal care products contribute to increasing cell migration and invasion, then reduction in exposure could offer a strategy for reducing breast cancer spread.

In Vitro Phytochemical Screening, Cytotoxicity Studies of Curcuma longa Extracts with Isolation and Characterisation of Their Isolated Compounds.

The Curcuma longa plant is endowed with multiple traditional and therapeutic utilities and is here explored for its phytochemical constituents and cytotoxic potential. Turmeric rhizomes were extracted from three different solvents and screened for the presence of different phytochemical constituents, observation of which indicated that the polar solvents favoured extraction of greater versatile phytochemical constituents. These extracts were investigated for their cytotoxic potential by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on three different of cell lines including SCC-29B (oral cancer cell line), DU-145 (prostate cancer cell line) and the Vero cell line (healthy cell line/non-cancerous cell line). This assay was performed by taking three extracts from isolated curcuminoids and a pure bioactive compound bisdemethoxycurcumin (BD). Bisdemethoxycurcumin was isolated from curcuminoids and purified by column and thin-layer chromatography, and its structural characterisation was performed with different spectroscopic techniques such as FTIR, NMR (1H Proton and 13C Carbon-NMR) and LC-MS. Amongst the extracts, the ethanolic extracts exhibited stronger cytotoxic potential against the oral cancer cell line (SCC-29B) with an IC50value of 11.27 µg/mL, and that this was too low of a cytotoxicity against the Vero cell line. Although, curcuminoids have also shown a comparable cytotoxic potential against SCC-29B (IC50 value 16.79 µg/mL), it was not as potent against the ethanolic extract, and it was even found to be cytotoxic against healthy cell lines at a very low dose. While considering the isolated compound, bisdemethoxycurcumin, it also possessed a cytotoxic potential against the prostate cancer cell line (DU-145) (IC50 value of 93.28 µg/mL), but was quite safe for the healthy cell line in comparison to doxorubicin.

Niacin deficiency modulates genes involved in cancer: Are smokers at higher risk?

The role of niacin's metabolite, nicotinamide adenine dinucleotide (NAD), in DNA repair via base-excision repair pathway is well documented. We evaluated if niacin deficiency results in genetic instability in normal human fetal lung fibroblasts (MRC-5), and further, does it leads to enhanced accumulation of cigarette smoke-induced genetic damage? MRC-5 cells were grown discretely in niacin-proficient/deficient media, and exposed to nicotine-derived nitrosamine ketone (NNK, a cigarette smoke carcinogen). Niacin deficiency abated the NAD polymerization, augmented the spontaneous induction of micronuclei (MN) and chromosomal aberrations (CA) and raised the expression of 10 genes and suppressed 12 genes involved in different biological functions. NNK exposure resulted in genetic damage as measured by the induction of MN and CA in cells grown in niacin-proficient medium, but the damage became practically marked when niacin-deficient cells were exposed to NNK. NNK exposure raised the expression of 16 genes and suppressed the expression of 56 genes in cells grown in niacin-proficient medium. NNK exposure to niacin-deficient cells raised the expression of eight genes including genes crucial in promoting cancer such as FGFR3 and DUSP1 and suppressed the expression of 33 genes, including genes crucial in preventing the onset and progression of cancer like RASSF2, JUP, and IL24, in comparison with the cells grown in niacin-proficient medium. Overall, niacin deficiency interferes with the DNA damage repair process induced by chemical carcinogens like NNK, and niacin-deficient population are at the higher risk of genetic instability caused by cigarette smoke carcinogen NNK.

Exposure to cyclic volatile methylsiloxanes (cVMS) causes anchorage-independent growth and reduction of BRCA1 in non-transformed human breast epithelial cells.

Dermal absorption of components of personal care products (PCPs) may contribute to breast cancer development. Cyclic volatile methylsiloxanes (cVMS) are used widely in the formulation of PCPs, and their presence has been recently detected in human blood. The objectives of this study were to investigate any genotoxic effects after short- (1 week) or longer-term (30 weeks) exposure to hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4) or decamethylcyclopentasiloxane (D5) in MCF-10 A and MCF-10F immortalized non-transformed human breast epithelial cells. Genotoxic effects were assessed by an ability of cells to grow in suspension culture, from DNA damage measured by comet assays, and from a reduction in levels of DNA repair proteins measured by RT-PCR and western immunoblotting. Dose-dependent anchorage-independent growth in methocel culture was observed after exposure to D3 (10-13 M-10-5 M) and D4/D5 (10-9 M-10-5 M). DNA damage was measured by the comet assay after 1-h exposure to D3 (10-6 M-10-5 M) and D4 (10-5 M). BRCA1 mRNA and BRCA1 protein levels were reduced after 30-week exposure to 10-5 M D4 and D5 in both cell lines. Reduced levels of mRNAs for other DNA repair proteins (BRCA2, ATM, ATR, CHK1 and CHK2) were also observed after exposure to 10-5 M D5 in both cell lines, and some reductions after exposure to D3 and D4. If cVMS can not only enable anchorage-independent growth of non-transformed breast epithelial cells and damage DNA, but also compromise DNA repair systems, then there is the potential for them to impact on breast carcinogenesis. Further risk assessment now requires information concerning the extent to which cVMS may be present in human breast tissues. Copyright © 2016 John Wiley & Sons, Ltd.

Association of genetic predisposition studies in CYP1A1 polymorphism studies in acute myeloid leukemia.

Cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) gene is one of the sub-members of CYP450 family member and it encodes with the families of drug metabolizing enzyme families along with the cancers and leukemias. Among leukemias, AML is considered to be one of the important leukemia which attack the older adults. The aim of this study is to explore the role of A4889G polymorphism in CYP1A1 gene in acute myeloid leukemia (AML) in the Saudi population. This study was designed as an experimental case-control study in which 100 AML cases and 100 controls were selected. This in vivo study was carried out using genomic DNA extraction, polymerase chain reaction and agarose gel electrophoresis and then BsrDI restriction enzyme to digest the A4889G polymorphism of the PCR products. In this study, 200 subjects were digested and based on the appearance of the bands, genotypes were categorized. The attained data was used to calculate the clinical details as well as genotype analysis. The study results confirmed AG genotype (OR = 3.23, CI = 1.60-6.55, p = 0.0008), AG + GG (OR = 3.47, CI = 1.76-6.86, p = 0.0002) and GG + AA (OR = 12.47, CI = 6.18-15.17, p < 0.0001) and G vs A (OR = 3.15, CI = 1.71-5.81, p = 0.0001) were associated in AML cases. In conclusion, we confirm that A4889G polymorphism is associated with AML in the Saudi population.

Bibliometric Analysis of Machine Learning Applications in Ischemia Research.

OBJECTIVE: The objective of this study is to conduct a comprehensive bibliometric analysis to elucidate the landscape of machine learning applications in ischemia research. METHODS: The analysis can be divided in three sections: part 1 scrutinizes articles and reviews with "ischemia" in their titles, while part 2 further narrows the focus to publications containing both "ischemia" and "machine learning" in their titles. Additionally, part 3 delves into the examination of the top 50 most cited papers, exploring their thematic focus and co-word dynamics. RESULTS: The findings reveal a significant increase in publications over the years, with notable trends identified through detailed analysis. The growth in publication counts over time, the leading contributors, institutions, geographical distribution of research output and journals are numerically presented for part 1 and part 2. For the top 50 most cited papers the dynamics of co-words, which offer a nuanced understanding of thematic trends and emerging concepts, are presented. Based on the number of citations the top 10 authors were selected, and later for each, total number of publications, h-index, g-index and m-index are provided. Additionally, figures depicting the co-authorship network among authors, departments, and countries involved in the top 50 cited papers may enrich our comprehension of collaborative networks in ischemia research. CONCLUSION: This comprehensive bibliometric analysis provides valuable insights into the evolving landscape of machine learning applications in ischemia research.

Evaluation of Biochemical Characteristics in a Retrospective Cohort of COVID-19 Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has had a significant impact on global health and healthcare systems. This retrospective study aimed to assess the association between biochemical parameters and outcomes in COVID-19 patients in Jazan, Saudi Arabia. METHODS: After establishing the inclusion criteria and obtaining ethical approval, data from 156 reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed COVID-19 patients were collected from electronic medical records from a general hospital in Samtah, Jazan, from April 2020 to October 2021. The collected data included patient demographics and liver, kidney, heart, and electrolyte function marker levels. Descriptive, inferential, and principal component analyses were conducted. RESULTS: Survival rates varied according to age and body mass index (BMI). Statistical analysis demonstrated that the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), sodium (Na), potassium (K), blood urea nitrogen (BUN), creatinine (Cr), creatine kinase (CK), CK myocardial band (MB), and lactate dehydrogenase (LDH) were significantly higher (P < 0.05) than the reference values, as assessed using the one-sample t-test. Principal component analysis (PCA) also revealed an underlying pattern in the variation of these biochemical markers. These findings suggest that certain biochemical parameters may serve as useful indicators for monitoring the condition of COVID-19 patients. CONCLUSION: This retrospective study in Jazan, Saudi Arabia highlights the association between biochemical parameters and outcomes in COVID-19 patients. Elevated levels of markers of liver, kidney, heart, and electrolyte function suggest organ damage and dysregulation. The pattern identified through PCA provides insights into disease severity. Monitoring these parameters may serve as valuable indicators for assessing COVID-19 patients. Further research is needed to validate these findings, explore their potential for personalized treatment strategies, and improve patient outcomes during the ongoing pandemic.

Cancer research in the United Arab Emirates from birth to present: A bibliometric analysis.

Background: Accumulating evidence indicates that the incidence of cancer is increasing in the United Arab Emirates (UAE). This analysis aimed to determine the current cancer research output in the UAE to guide future national research. Methods: The Scopus database was searched for cancer-related bibliographic data from the UAE. The number of publications, citation analysis, co-authorship of the author, institution, and country, keyword co-occurrence, and reference co-citations were analyzed using the R-studio bibliometrics package and VOSviewer software. Results: A total of 1678 journal articles were retrieved from 1981 to 2022. Cancer research in the UAE (UCR) is increasing at a rate of 14.64% (R-squared = 0.75; F = 46.477; P<0.001). The UAE had a 0.06% participation rate in terms of the number of original articles. The rate of international co-authorship is 40.23%. The U.S.A., U.K., Egypt, Saudi Arabia, India, and Canada had more than 100 co-authored documents from 156 countries that collaborated with the U.A.E. Conclusions: Compared to other nations, the UAE has fewer publications on cancer, although the number is growing. The current report provides an up-to-date and in-depth summary of the trends in UCR. This project is an excellent place for researchers interested in conducting data-mapping work in this field.

Coffee arabica research (1932-2023): Performance, thematic evolution and mapping, global landscape, and emerging trends.

Background: Research on Coffea arabica focuses on various aspects, including genetics, breeding, climate change resilience, pest and disease management, agronomy, sensory analysis, and sustainability. This study aims to analyze the hotspots, conceptual map and dynamicity, global landscape, and emerging trends in Coffea arabica research (CA-R). Methods: A comprehensive dataset comprising data-driven articles (N = 3967) from 1932 to 2023 was extracted from Scopus using predefined search terms. VOSviewer and Bibliometrix applications were utilized to analyze the data. Thematic evolution was examined by identifying shifts in research focus over time. The global landscape was assessed by examining comparative productivity and collaborative dynamics. Highly-cited CA-R was identified to highlight key findings in specific research areas. Results: The analysis revealed a steady growth of CA-R (annual growth rate = 6.53 %), with strong international collaboration (international co-authorships = 29.35 %) and significant contributions from various countries. Brazil leads the way with 1601 publications, accounting for 28.55 % of the total. Recognizable CA-R focused on important areas such as pollination, shade management, nanotechnology applications, roasting effects, disease management, and environmental impacts. Thematic analysis identified five distinct clusters representing different CA-R themes: "coffee", "coffea," "fermentation," "Coffea arabica," and "climate change." Emerging themes such as "in vitro culture," "sustainable agriculture," "climate change," and "coffee berry borer" were also identified. Conclusion: The current findings enhance our understanding of CA-R and lay the groundwork for future studies in the coffee industry.

Robotic surgery: bibliometric analysis, continental distribution, and co-words analysis from 2001 to 2023.

The project aimed to conduct an up-to-date and comprehensive bibliometric analysis of robotic surgery to provide a detailed and holistic understanding of the field. Three strategies were employed in the data analysis i.e. search terms were explored in (A) the title, abstract, and keywords and (B) only in the title of the documents. In 3rd part we analyzed the top 100 most cited papers. Vosviewer and R Studio were utilized for detailed bibliometric and network analyses. Strategy one identified 38,469 publications, and strategy two identified 6451 publications from 2001 to 2023. The top authors, universities, countries, sponsors, and sources based on the number of publications were identified for both strategies. The top 100 most cited papers were analyzed, providing the annual number of publications and various citation metrics. Top authors (by number of publications, total citations, h-index, g-index, and m-index), universities, and countries within these highly cited papers, along with their co-authorship networks and dynamics, were examined. Co-words analysis of the top 100 most cited papers revealed the primary focus of these documents across 25 categories. This comprehensive bibliometric analysis of robotic surgery highlighted significant contributions and collaborations in the field, emphasizing the importance of global and collaborative efforts in advancing robotic surgery research.

Top 1000 Most Cited Papers in World Neurosurgery.

BACKGROUND: Over the past 15 years, WORLD NEUROSURGERY (WN) has emerged as a pivotal source in the neurosurgery field, reflecting remarkable growth and development. Originally published as Surgical Neurology from 1973 to 2009, the journal transitioned to its current title in 2010, significantly expanding its reach and influence. METHODS: A comprehensive bibliometric analysis of WN's publications from 1973 to 2023 was performed. The analysis focused on identifying the top authors, universities, countries, and sponsors in 2 periods: 1973-2009 and 2010-2023. Additionally, the study included a detailed examination of the top 1000 most cited papers, and summary of top 10 most cited papers. RESULTS: The analysis revealed that during the Surgical Neurology period, 6567 research documents were published, including 6503 articles and 64 reviews. Since rebranding as WN, the journal has published an additional 17,663 documents, comprising 15,366 articles and 2297 reviews up to 2023. The top contributors (authors, universities, and sponsors) were identified, and the study found that WN has successfully increased its foothold across various continents. The co-word analysis provided insights into the thematic focus of the top 1000 most cited papers, categorizing them into 15 distinct areas. CONCLUSIONS: This study underscores WN's significant role in advancing neurosurgical research over the past 5 null decades. The findings highlight the journal's evolution, its expanding global influence, and the key contributors to its success.

Risk of acute coronary syndrome and relationship with the use of khat and tobacco products in the Jazan region, Saudi Arabia: A prospective case-control study.

INTRODUCTION: Previous studies have identified several risk factors for acute coronary syndrome (ACS). This study was intended to examine the potential risk of ACS associated with khat and tobacco use. METHODS: A case-control study of 344 people (172 cases and 172 controls) was conducted at Prince Mohammed Bin Nasser Hospital in Jazan, Saudi Arabia, from April to September 2019. The cases and controls were matched for age (±5 years) and gender. Data were analyzed using descriptive, inferential, and modeling analyses. We utilized the adjusted odds ratio (AOR) to express the results. RESULTS: The prevalence of ever khat chewing among all study participants was 29.1%, significantly higher for the cases with ACS than for the control group (43.6% vs 14.5%, p<0.001). Cigarette smokers accounted for 33.4% of the study participants, and 22.1% were ACS cases, which is a significantly higher percentage than the control group. The prevalence of smokeless tobacco was 20.3% among ACS cases and 14.5% among controls, with no statistically significant differences (p>0.05). In the final model, tobacco use was more likely to be reported among cases with myocardial infarction (MI) (AOR=4.58; 95% CI: 1.01-4.73, p<0.05) as was khat chewing (AOR=3.4; 95% CI: 1.55-7.46, p<0.05), after controlling for other traditional risk factors. CONCLUSIONS: Khat chewing was reported more by those who reported ACS. ACS cases were more likely to be frequent khat users with chewing sessions of five or more days per week. Regular tobacco use was also reported in those who reported ACS, and this increases with the amount of tobacco used. Implementing early intervention strategies can help mitigate the impact of khat chewing and smoking on the development of ACS.

Cetuximab-conjugated sodium selenite nanoparticles for doxorubicin targeted delivery against MCF-7 breast cancer cells.

Aim: To develop and characterize doxorubicin-loaded sodium selenite nanoparticles (SSNP-DOX) and their surface attachment with cetuximab (mAb-SSNP-DOX).Methods: SSNP-DOX was formulated by gelation and then conjugated with cetuximab to form mAb-SSNP-DOX. Characterization included DLS, SEM, TEM, DSC, Raman spectroscopy and XRD. In vitro, the kinetics of doxorubicin release and cytotoxicity in MCF-7 breast cancer cells were investigated.Results: The zeta potential for SSNP-DOX and mAb-SSNP-DOX was -14.4 ± 10.1 mV and -27.5 ± 7.28 mV, with particle sizes of 181.3 nm and 227.5 nm, respectively. The formulation intensity was 89.7% for SSNP-DOX and 100% for mAb-SSNP-DOX, with PDI values of 0.419 and 0.251, respectively. SEM and TEM showed that mAb-SSNP-DOX was smooth and spherical. The DSC analysis revealed exothermic peaks at 102.44°C for SSNP-DOX and 144.21°C for mAb-SSNP-DOX, along with endothermic peaks at 269.19°C and 241.6°C, respectively. Raman spectroscopy showed a higher intensity for mAb-SSNP-DOX. The XRD study showed different peaks for each formulation. Both followed zero order kinetics for doxorubicin release. Cytotoxicity studies showed significant effects and high apoptosis in MCF-7 cells for both formulations.Conclusion: The mAb-SSNP-DOX showed promising properties, more effective doxorubicin release and higher cytotoxicity against breast cancer cells compared with SSNP-DOX.

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Safety and efficacy of stem cell therapy for Crohn's disease: An umbrella review of systematic reviews.

BACKGROUND: Crohn's disease is a chronic, relapsing form of inflammatory bowel disease marked by severe gastrointestinal inflammation and a broad range of debilitating symptoms. Despite advances in medical treatments, achieving sustained remission remains challenging for many patients. This umbrella review aims to consolidate evidence from various systematic reviews to evaluate the efficacy and safety of stem cell therapies in treating Crohn's disease. METHODS: This review followed the Joanna Briggs Institute methodology and adhered to PRISMA guidelines. A literature search of PubMed, Web of Science, Embase, and the Cochrane Library covered records up to April 20, 2024. Only systematic reviews and meta-analyses on stem cell therapy for Crohn's disease were considered. Data were extracted and analyzed for clinical efficacy indicators like remission induction and safety metrics, including adverse events and mortality rates. RESULTS: Sixteen systematic reviews were included, spanning studies conducted between 2009 and 2023. Stem cell therapy showed a pooled risk ratio (RR) of 1.299 (95% CI: 1.192 to 1.420) for clinical remission, indicating a 29.9% increased likelihood of remission compared to controls. The pooled RR for healing perianal Crohn's disease was 1.358 (95% CI: 1.13 to 1.631), suggesting a 35.8% increased likelihood of healing. A pooled RR of 1.481 (95% CI: 1.036 to 2.116) shows a 48.1% higher immediate fistula closure rate with stem cell therapy. For long-term outcomes, a RR of 1.422 (95% CI: 1.091 to 1.854) indicates a 42.2% increased likelihood of maintaining closure. However, stem cell therapy did not significantly impact Crohn's Disease Activity Index (CDAI) (RR: 1.154, 95% CI: 0.193 to 6.883) and Perianal Disease Activity Index (PDAI) scores (mean difference at 12 weeks: -0.505, 95% CI: -2.481 to 1.471; mean difference at 24 weeks: -0.338, 95% CI: -1.638 to 0.963). The safety profile was comparable to conventional therapies, with a pooled RR of 0.972 (95% CI: 0.739 to 1.278) for adverse events and 1.136 (95% CI: 0.821 to 1.572) for serious adverse events. CONCLUSION: Stem cell therapy offers significant progress in treating Crohn's disease, particularly in complex cases, by improving fistula closure rates and suggesting potential as a supplementary therapy. Its safety profile aligns with conventional treatments, yet ongoing clinical trials are crucial to optimize its use. Continual research will enable healthcare providers to tailor more effective treatment strategies for this challenging condition.

A case-control study in NAT2 gene polymorphism studies in patients diagnosed with acute myeloid leukemia.

INTRODUCTION: Acute myeloid leukemia (AML) is a clinically defined heterogeneous disease whose pathophysiology is currently unknown. The association of NAT2 acetylation profiles with human cancer risks, particularly with AML, was investigated in molecular epidemiological studies. Additionally, the NAT2 gene was carried out with acute lymphoid leukemia and other cancers. AIM: In this case-control study, C481T (rs1799929) and G857A (rs1799931) polymorphism studies were investigated in diagnosed AML patients in the Saudi population. METHODS: This case-control study included 100 AML patients and 100 control subjects recruited in Saudi Arabia. The C481T and G857A polymorphisms were genotyped using specific primers and restriction enzymes. Statistical analysis was performed on the AML patients and controls using chi-square tests, genotyping, and allele frequencies (odds ratios, 95% of confidence intervals, and P-values). RESULTS: Hardy Weinberg Equilibrium was determined to be both within and outside of the G857A and C481T polymorphisms. The allele and genotyping frequencies in AML and control subjects were analyzed, and the results corroborated the unfavorable connection with C481T (CC vs CT+TT; OR-1.12; (95% CIs: 0.64-1.96); P=0.67 and T vs C; OR-0.89; (95% CIs: 0.59-1.35) and P=0.60) and G857A polymorphisms (GG vs GA+AA; OR-1.50; (95% CIs: 0.83-2.71); P=0.17 and A vs G; OR-0.71; (95%CIs: 0.43-1.19) and P=0.19) in the NAT2 gene. CONCLUSION: The study results revealed a negative correlation as well as a protective factor for AML with the C481T and G857A polymorphisms in the NAT2 gene.

HDAC inhibition by Nigella sativa L. sprouts extract in hepatocellular carcinoma: an approach to study anti-cancer potential.

A wide variety of natural products have been widely used in chemoprevention therapy because they have antioxidant, anti-inflammatory, and anticancer activity. In the present study, we shed light on the 5th day germinated sprouts of N. sativa seeds and evaluated them against HDAC inhibition and antioxidant activity. The extract from the seed and sprout was extracted and characterised by LC-MS/MS, FTIR, and NMR to reveal its chemical composition, especially thymol (THY) and thymoquinone (TQ). Hepatocellular carcinoma (HCC) is a global health concern as it is a major lifestyle disease. Hence, incorporating herbal-based therapeutic compounds into everyday routines has become an attractive alternative for preventing hepatic diseases. Histone deacetylase (HDAC) inhibition (HDACi) is emerging as a promising therapeutic strategy for managing various carcinomas including HCC. Therefore, the 5th day of N. sativa can be used as a potential anticancer agent by inhibiting HDAC activity, as it is reported to have an important role in the management of oxidative stress. The bioactive compound of N. sativa, i.e. thymoquinone, also showed a good binding affinity with the HDAC protein (3MAX) with a stable interaction in an in silico study as compared to the standard drug (Trichostatin A) and thymol.Communicated by Ramaswamy H. Sarma.

Screening of V617F mutation in JAK2 gene with acute myeloid leukemia in the Saudi population.

Progress in pathogenesis and therapy of acute myeloid leukemia (AML) is presently accelerating. The Janus kinase 2 gene (JAK2) mutations are rare in de novo AML. The gene codes for the tyrosine kinase that has a significant role in the signal transduction in hematopoietic cells. The aim of this study was to induce V617F mutation in the JAK2 gene in the AML patients diagnosed in the Saudi population. In this case-control study, 100 AML patients and 100 healthy controls were recruited. Genotyping was performed with polymerase chain reaction followed with restriction fragment length polymorphism analysis. The mean age of the AML patients and healthy controls was found to be almost similar (p=0.60). In this study, 15% of VF mutation was documented in the AML cases and none of the mutations were documented either in FF mutation in AML cases or VF and FF mutations in the healthy control subjects. VF mutations [VF vs VV; OR-18.79; (95%CIs: 2.442-144.6) and p=0.0001; F vs V; OR-87.76; (95% CIs: 11.76-654.7) and p<0.0001] were found to be significantly associated when compared between AML cases and healthy controls. In conclusion, the V617F mutation showed the positive association in the AML patients diagnosed in the Saudi population.