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Cisplatin is an efficient anticancer drug against various types of cancers however, its usage involves side effects. We investigated the mechanisms of action of indole derivative, 2-(5-methoxy-2-methyl-1H-indol-3-yl)-N'-[(E)-(3-nitrophenyl) methylidene] acetohydrazide (MMINA) against anticancer drug (cisplatin) induced organ damage using a rodent model. MMINA treatment reversed Cisplatin-induced NO and malondialdehyde (MDA) augmentation while boosted the activity of glutathione peroxidase (GPx), and superoxide dismutase (SOD). The animals were divided into five groups ( n  = 7). Group1: Control (Normal) group, Group 2: DMSO group, Group 3: cisplatin group, Group 4: cisplatin + MMINA group, Group 5: MMINA group. MMINA treatment normalized plasma levels of biochemical enzymes. We observed a significant decrease in CD4 + COX-2, STAT3, and TNF-α cell population in whole blood after MMINA dosage. MMINA downregulated the expression of various signal transduction pathways regulating the genes involved in inflammation i.e. NF-κB, STAT-3, IL-1, COX-2, iNOS, and TNF-α . The protein expression of these regulatory factors was also downregulated in the liver, kidney, heart, and brain. In silico docking and dynamic simulations data were in agreement with the experimental findings. The physiochemical properties of MMINA predicted it as a good drug-like molecule and its mechanism of action is predictably through inhibition of ROS and inflammation.

This study aimed to explore the mechanisms of action of a sulindac acetohydrazide derivative, N'-(4-dimethylaminobenzylidene)-2-1-(4-(methylsulfinyl) benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide, against anticancer drug cisplatin induced organ damage. Using a rodent model, various markers of organ function and signaling pathways were examined and validated by molecular docking studies. The study involves five groups of animals: control, DMSO, CDDP, CDDP + DMFM, and DMFM. Biochemical enzyme activity, histopathology, tissue antioxidant, and oxidative stress markers were examined. RT-PCR and western blot analyses were conducted for the expression of inducible cyclooxygenase enzyme (COX-2), nuclear factor kappa beta (NF-κB), p65, IL-1, TNF-α, and inducible nitric oxide synthase (iNOS). Flow cytometry analysis of CD4 + TNF-α, CD4 + COX-2, and CD4 + STAT-3 cells in whole blood was performed. Structural and dynamic behavior of DMFM upon binding with receptor molecule molecular docking and dynamic simulations were performed using bioinformatics tools and software. Treatment with DMFM reversed cisplatin-induced malondialdehyde (MDA) and nitric oxide (NO) induction, whereas the activity of glutathione peroxidase (GPx), and superoxide dismutase (SOD) in the kidney, heart, liver, and brain tissues were increased. DMFM administration normalized plasma levels of biochemical enzymes. We observed a marked decline in CD4 + STAT3, TNF-α, and COX2 cell populations in whole blood after treatment with DMFM. DMFM downregulated the expression factors related to inflammation at the mRNA and protein levels, i.e., IL-1, TNF-α, iNOS, NF-κB, STAT-3, and COX-2. Dynamic simulations and in silico docking data supports the experimental findings. Our experimental and in silico results illustrated that DMFM may affect protective action against cisplatin-induced brain, heart, liver, and kidney damage via reduction of inflammation and ROS.

Cisplatin is an efficient anticancer drug against various types of cancers however, its usage involves side effects. We investigated the mechanisms of action of indole derivative, 2-(5-methoxy-2-methyl-1H-indol-3-yl)-N'-[(E)-(3-nitrophenyl) methylidene] acetohydrazide (MMINA) against anticancer drug (cisplatin) induced organ damage using a rodent model. MMINA treatment reversed Cisplatin-induced NO and malondialdehyde (MDA) augmentation while boosted the activity of glutathione peroxidase (GPx), and superoxide dismutase (SOD). The animals were divided into five groups (n = 7). Group1: Control (Normal) group, Group 2: DMSO group, Group 3: cisplatin group, Group 4: cisplatin + MMINA group, Group 5: MMINA group. MMINA treatment normalized plasma levels of biochemical enzymes. We observed a significant decrease in CD4+COX-2, STAT3, and TNF-α cell population in whole blood after MMINA dosage. MMINA downregulated the expression of various signal transduction pathways regulating the genes involved in inflammation i.e. NF-κB, STAT-3, IL-1, COX-2, iNOS, and TNF-α. The protein expression of these regulatory factors was also downregulated in the liver, kidney, heart, and brain. In silico docking and dynamic simulations data were in agreement with the experimental findings. The physiochemical properties of MMINA predicted it as a good drug-like molecule and its mechanism of action is predictably through inhibition of ROS and inflammation.Cisplatin is an efficient anticancer drug against various types of cancers however, its usage involves side effects. We investigated the mechanisms of action of indole derivative, 2-(5-methoxy-2-methyl-1H-indol-3-yl)-N'-[(E)-(3-nitrophenyl) methylidene] acetohydrazide (MMINA) against anticancer drug (cisplatin) induced organ damage using a rodent model. MMINA treatment reversed Cisplatin-induced NO and malondialdehyde (MDA) augmentation while boosted the activity of glutathione peroxidase (GPx), and superoxide dismutase (SOD). The animals were divided into five groups (n = 7). Group1: Control (Normal) group, Group 2: DMSO group, Group 3: cisplatin group, Group 4: cisplatin + MMINA group, Group 5: MMINA group. MMINA treatment normalized plasma levels of biochemical enzymes. We observed a significant decrease in CD4+COX-2, STAT3, and TNF-α cell population in whole blood after MMINA dosage. MMINA downregulated the expression of various signal transduction pathways regulating the genes involved in inflammation i.e. NF-κB, STAT-3, IL-1, COX-2, iNOS, and TNF-α. The protein expression of these regulatory factors was also downregulated in the liver, kidney, heart, and brain. In silico docking and dynamic simulations data were in agreement with the experimental findings. The physiochemical properties of MMINA predicted it as a good drug-like molecule and its mechanism of action is predictably through inhibition of ROS and inflammation.

ObjectivesHysterectomy, a common surgical procedure, is frequently associated with moderate-to-severe postoperative pain and a high incidence of postoperative nausea and vomiting (PONV). Dexamethasone, a corticosteroid, may help alleviate these symptoms; however, existing evidence is largely drawn from mixed surgical populations and does not specifically address its efficacy and safety in hysterectomy patients. This meta-analysis provides a focused and updated synthesis of randomised controlled trials (RCTs) in this population, incorporating time-stratified pain outcomes and subgroup analyses by dose, surgical approach, timing and route of administration to evaluate the role of dexamethasone in postoperative recovery.DesignSystematic review and meta-analysis using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.Data sourcesPubMed, Scopus, Google Scholar and The Cochrane Central Register of Controlled Trials (CENTRAL) were searched through 1 November 2024.Eligibility criteria for selecting studiesWe included RCTs comparing dexamethasone with placebo for postoperative outcomes in hysterectomy patients.Data extraction and synthesisTwo independent reviewers used standardised methods to search, screen and code included studies. Risk of bias was assessed using the Cochrane Collaboration and Evidence Project tools. Meta-analysis was conducted using random effects models. Findings were summarised in GRADE evidence profiles and synthesised qualitatively.Results15 RCTs (1362 patients) were included. Dexamethasone significantly reduced PONV (risk ratio (RR): 0.53, 95% CI 0.47 to 0.61, p<0.00001, I2: 0% high certainty) and pain scores at 24 hours (mean difference (MD): −0.20, 95% CI −0.35 to −0.05, p=0.009, I²=0%, moderate certainty), 8–12 hours (MD: −0.60, 95% CI −0.88 to −0.31, p<0.0001, I2: 27%, moderate certainty and 4 hours (MD: −0.43, 95% CI −1.07 to 0.21, p=0.19, 93%, moderate certainty). It also decreased the use of rescue antiemetics (RR: 0.57, 95% CI 0.43 to 0.75, I2: 39%, high certainty) and postoperative opioid consumption (standardised MD: −0.48, 95% CI −0.90 to −0.05, p=0.03, I2: 74%, low certainty). The effects of rescue analgesics and hospital stay duration were nonsignificant. Subgroup analyses showed consistent antiemetic efficacy of dexamethasone across doses, timings, routes and procedures. For pain, greater analgesic effects were seen with higher doses and perineural administration, particularly at 8–12 hours. The risk of bias was low in most studies, but evidence of publication bias was observed for the pain score outcome.ConclusionsDexamethasone is an effective adjunct in hysterectomy, significantly reducing PONV and postoperative pain at 8–12 and 24 hours, particularly with 4–10 mg doses. Benefits are consistent across routes, timings and surgical approaches, with greater early analgesia after perineural use. It reduces opioid consumption but has a limited effect on rescue analgesia, supporting its role as a complementary analgesic. While generally considered safe, current safety data are limited, highlighting the need for further research. These results support its use in multimodal recovery protocols and identify priorities for future studies in high-risk and diverse surgical populations.PROSPERO registration numberCRD42024608067.

Criminals often attempt to conceal blood-stained weapons used in violent crimes, making forensic evidence crucial in solving cases. This study explores the recovery and extraction of trace DNA from sports equipment, including cricket bats, table tennis racquets, and hockey sticks, which are frequently implicated in such incidents. Our research evaluates various double swab collection methods for retrieving trace DNA from these sports items, emphasizing those associated with blunt force trauma. We also compare presumptive and confirmatory tests to establish a direct correlation. This research consistently demonstrated robust DNA recovery, surpassing a 50 % threshold across all tests. Specifically, DNA recovery from buried samples reached an impressive 87 %, while washed samples still yielded a substantial 80 % efficiency. We conducted a comparative analysis between presumptive and confirmatory testing methods, establishing a direct correlation between the two. Variability in DNA recovery efficiency was observed and attributed to factors like the type of surface the items contacted, and ambient humidity levels. In addition to presenting robust DNA recovery rates, statistical analyses were employed to compare methods, establishing correlations and highlighting the influence of environmental factors on DNA recovery efficiency. These findings have significant implications for forensic investigations involving silent weapons crafted from sports equipment, emphasizing the need for standardized protocols and consideration of environmental factors in DNA analysis. •Substrate surface crucially influences DNA deposition and recovery.•Adequate fresh DNA found in washed and buried objects.•Initial DNA amount reduces over time in both washed and buried cases.•A few cells can be enough to generate DNA profile.•This research advances forensic science, particularly in detection applications.

Background: BReast CAncer gene 2 (BRCA2), a tumor suppressor gene located on chromosome 13q, encodes a 384-kDa protein which activates homologous recombination pathway to repair ssDNA damage. Aims and Objectives: Keeping in view the high prevalence of breast cancer in Pakistan and significant association of BRCA2 with breast cancer, this project was initiated to investigate the mutational status of BRCA2 in Pakistani breast cancer patients. Materials and Methods: For this purpose, blood samples of 45 individuals, including 24 female patients (infiltrating ductal carcinoma of breast), who visited Institute of Nuclear Medicine, Oncology and Radiotherapy Hospital and Ayub Medical Complex, Abbottabad, Khyber Pakhtunkhwa, and 21 normal female residents of the area were collected and processed to extract deoxyribonucleic acid (DNA). Different regions of BRCA2 exon 11 were amplified through polymerase chain reaction (PCR), and PCR-amplified products of one (NF45) normal sample and four cancerous (205BC, 215BC, 218BC, 222BC) samples were subjected to DNA sequence analysis. Results: Analysis of retrieved sequences revealed one novel nonsense mutation in sample 205BC. The observed mutation (delA21587) shifted the normal frame of amino acid (N905I, T906L, K907R, E908N, L909F, H910M, E911K, T912Q, and D913T) in encoded mutant protein and converted L914 into premature termination codon. In case of sample 222BC, another novel substitution mutation (A>G24962) was observed, which altered codon of I (isoleucine) into the codon for M (methionine) at position 2040 in resultant mutant protein. Conclusion: The results reflect the unique mutational profile of BRCA2 in Pakistani infiltrating ductal carcinoma patients and suggest an extension of study on a large scale.

The present study was aimed to evaluate the effects of wheat germ oil and wheat bran fiber as fat replacers on quality and stability of low‐fat beef patties. Total five treatments were prepared by employing wheat germ oil (WGO) and wheat bran fiber (WBF). WBF was used at fixed amount of 3% in all treatments except control in conjunction with varying WGO concentrations as follows: 1.5%, 3%, and 4.5%. Prepared raw and cooked beef patties were stored at 4°C, and further analyses were carried out up to 21 days of storage period with intermittent evaluation interval of 7 days. Higher values of TBARS, peroxide, and cholesterol were observed in raw and cooked beef patties in control, whereas minimum values were found in treatment of beef patties prepared with WGO 4.5% + WBF 3%. The physicochemical parameters were observed by pH and hunter color values. pH was higher in cooked patties as compared to beef patties and showed increases with increase in WGO concentration and storage intervals. The sensorial attributes were observed which included different parameters, such as appearance, texture, taste, odor, and overall acceptability. Higher score was given by the panelists to control for both raw and cooked beef patties; however, minimum score for all sensory properties was found in group treated with WGO 4.5% + WBF 3% within acceptable limit. In nutshell, raw and cooked beef patties treated with WGO 4.5% plus WBF 3% showed better quality, stability, and reduced cholesterol content. In nutshell, raw and cooked beef patties treated with wheat germ oil 4.5% plus wheat bran fiber 3% showed better quality, stability, and reduced cholesterol content.