Proteobacterial Antimicrobial Compound Efflux (PACE) family proteins are one of seven types of multidrug efflux pumps in Gram-negative bacteria. PACE proteins can actively efflux synthetic biocides, including the antiseptic chlorhexidine, whilst their physiological substrates are polyamines. PACE proteins contain four putative transmembrane-spanning alpha-helices, and experimental evidence suggests that they mainly exist and function in a dimeric state, but the high-resolution structural organisation and molecular mechanism of PACE proteins are yet to be elucidated experimentally. As an essential first step to achieve this, we employed a strategy for gene cloning, expression screening and large-scale purification of representative PACE proteins. The genes of 24 proteins were successfully cloned into IPTG-inducible plasmid pTTQ18 directly upstream from a His6-tag coding sequence and transformed into E. coli BL21(DE3) cells. Small-scale expression tests identified seven proteins amplified at a sufficient level for larger-scale cultures and purification. Based on results from 30-litre fermentor cultures and inner membrane preparations, four proteins (A1S_2063, Fbal_3166, STY_3166, Tmarg_opt) representing distinct phylogenetic groups of the PACE family, were progressed to detergent solubilisation and purification. These proteins had purities of 86, 84, 80 and 78%, and purification yields of 1.1, 1.1, 1.3 and 1.0 mg/litre cell culture, respectively. The detergent-solubilised purified proteins had far-UV circular dichroism spectra consistent with alpha-helical secondary structure, producing melting temperatures of 46.7, 34.2, 32.6 and 37.6 C, respectively. A1S_2063 was most stable and might be best for structure elucidation. Secondary structure in all purified proteins appeared reasonably stable for performing biochemical and biophysical experiments up to 25 C.

Background: Non-small cell lung cancer (NSCLC) represents nearly 85% of lung cancer cases globally and remains a major cause of cancer mortality. Although immune checkpoint inhibitors improve survival, durable responses occur in a limited number of patients, highlighting the urgent need for reliable, minimally invasive predictive biomarkers. Objective: To evaluate whether specific serum protein signatures can predict clinical response to immune checkpoint inhibitors in patients with NSCLC. Methods: This prospective cohort study was conducted at National Institute of Cancer Research and Hospital, Dhaka, Bangladesh from January 2024 to December 2024. A total of 67 histologically confirmed NSCLC patients receiving ICI therapy were enrolled using purposive sampling. Baseline serum samples were obtained before treatment and analyzed for selected protein biomarkers related to immune regulation and inflammation. Clinical response was evaluated at 12 weeks using the RECIST criteria. Data were processed in SPSS 23.0, applying logistic regression and ROC curve analyses. Results: Of the 67 patients, 29 (43.3%) achieved partial response or stable disease, whereas 38 (56.7%) experienced disease progression. Higher baseline pro-inflammatory protein levels were significantly associated with poor response (p<0.05), while elevated immune-activating proteins predicted favorable outcomes (p<0.01). The combined serum protein signature showed strong predictive accuracy (AUC=0.81; 95% CI: 0.70–0.91). Conclusion: Distinct serum protein signatures may serve as non-invasive predictive biomarkers for clinical response to ICIs in NSCLC patients. These findings support further validation in larger, multicenter studies to optimize personalized immunotherapy strategies.

Cocaine (koe kane') is a potent local anesthetic that appears to act by inhibition of voltage-gated sodium channels, increasing the threshold for electric excitability of nerve axons and thus decreasing neuroconduction. In the central nervous system, cocaine appears to block both norepinephrine and serotonin reuptake. The aim of this study is to determine the histological effect of crack cocaine on the liver of adult albino wistar rat. A total of forty (40) adult Albino Wistar rats of comparable sizes were used for this study. They were divided into four equal groups (A – D) with ten (10) rats each. Group A served as the control and the rats were given distilled water and feed only. In addition to feed and water, groups B rats were given 0.5ml (100mg) crack cocaine extract and crack cocaine extract, group C rats were given 2ml (200mg) crack cocaine extract, and group D rats were given 5ml (300mg) crack cocaine extract respectively. The drug administration was given daily for 14 days (2 weeks) and the weights of both the test and control animals was monitored before and after administration of crack cocaine extract. The administration of the crack cocaine extracts was given orally. After the administration, the rats were put under light chloroform anaesthesia and the liver were obtained. ANOVA was used to analyze the results of the weight and differences was considered significant at p<0.05 level of confidence. All data was expressed in table as mean ± standard deviation (SD). The results of this study show presence of bridging necrosis and portal fibrosis in the liver histology of test wistar rats administered with crack cocaine at 200 and 300mg when compared with the non-cocaine administered group also a non-significant variation was observed in the body weight of control and test groups across the groups. In conclusion, the use of cocaine can lead to significant and harmful effects on liver histology, resulting from a combination of factors related to the drug's pharmacological actions, metabolism, and physiological responses. These changes stem from cocaine's vasoconstrictive properties, generation of reactive metabolites, direct toxic effects, and interactions with other substances.