Colorectal cancer (CRC), a major global health concern, necessitates innovative treatments. Chimeric antigen receptor (CAR) T cells have shown promises, yet they grapple with challenges. The spotlight pivots to the rising heroes: CAR natural killer (NK) cells, offering advantages such as higher safety profiles, cost-effectiveness, and efficacy against solid tumors. Nevertheless, the specific mechanisms underlying CAR NK cell trafficking and their interplay within the complex tumor microenvironment require further in-depth exploration. Herein, we provide insights into the design and engineering of CAR NK cells, antigen targets in CRC, and success in overcoming resistance mechanisms with an emphasis on the potential for clinical trials.
Colorectal Neoplasms/immunology* ; Humans ; Killer Cells, Natural/metabolism* ; Receptors, Chimeric Antigen/genetics* ; Immunotherapy, Adoptive/methods* ; Tumor Microenvironment/immunology* ; Animals

Enterococcus species are Gram-positive cocci normally found in the gut but have emerged as opportunistic pathogens in healthcare settings, with rising multidrug resistance, particularly vancomycin-resistant Enterococci (VRE) posing major therapeutic challenges. This study evaluated the antibacterial and synergistic effects of plant-derived stilbenes from Reynoutria japonica against clinical VRE isolates. Ten clinical Enterococcus faecalis isolates were identified using standard morphological, biochemical, and Gram-staining methods, and antibiotic susceptibility testing. The antibacterial activity of polydatin, resveratroloside, and trans-resveratrol was assessed by agar well diffusion, and evaluation of minimum inhibitory concentrations (MICs) and evaluation of bactericidal activity concentrations (MBCs), with synergistic effects tested in combination with vancomycin.Molecular docking was performed with DapF, vanA, and gelE proteins. All isolates were resistant to vancomycin, ampicillin, imipenem, gentamicin, and ciprofloxacin but sensitive to linezolid. All three stilbenes displayed antibacterial activity. Notably, trans-resveratrol was the most active compound, with a MIC value of 0.156 mM and bactericidal activity (an MBC value equal to the MIC). Furthermore, all compounds exhibited synergistic effects when combined with vancomycin. Phytochemical analysis confirmed these stilbenes as major constituents in the root extract of R. japonica. Molecular docking studies revealed strong binding affinities of the compounds to key virulence and resistance-associated proteins (DapF, VanA, and GelE). These results indicate that transresveratrol and related stilbenes are promising candidates for development as alternative or adjunct therapeutic agents against VRE infections. Additionally, this study substantiates the traditional use of R. japonica as a source of bioactive antimicrobial compounds.

Background: Racial and ethnic disparities in orthopedic surgery may be associated with worse perioperative complications. For patients with hip fractures, studies have shown that early surgery, typically within 24 to 48 hours of admission, may decrease postoperative morbidity and mortality. Our objective was to determine whether race is associated with longer time to surgery from hospital presentation and increased postoperative complications. Methods: We queried the National Surgical Quality Improvement Program database from 2011 to 2017 for patients (> 65 years) with hip fractures who underwent surgical fixation. Patients were identified using Current Procedural Terminology codes (27235, 27236, 27244, and 27245). Delayed surgery was defined as time to surgery from hospital admission that was greater than 48 hours. Time to surgery was compared between races using analysis of variance. A multivariate logistic regression analysis adjusting for comorbidities, age, sex, and surgery was performed to determine the likelihood of delayed surgery and rate of postoperative complications. Results: A total of 58,456 patients who underwent surgery for a hip fracture were included in this study. Seventy-two percent were female patients and the median age was 87 years. The median time to surgery across all patients was 24 hours. African Americans had the longest time to surgery (30.4 ± 27.6 hours) compared to Asians (26.5 ± 24.6 hours), whites (25.8 ± 23.4 hours), and other races (22.7 ± 22.0 hours) (p < 0.001). After adjusting for comorbidities, age, sex, and surgery, there was a 43% increase in the odds of delayed surgery among American Africans compared to whites (odds ratio, 1.43; 95% confidence interval, 1.29–1.58; p < 0.001). Despite higher odds of reintubation, pulmonary embolism, renal insufficiency or failure, and cardiac arrest in African Americans, mortality was significantly lower compared to white patients (4.41% vs. 6.02%, p < 0.001). Asian Americans had the lowest mortality rate (3.84%). Conclusions A significant disparity in time to surgery and perioperative complications was seen amongst different races with only African Americans having a longer time to surgery than whites. Further study is needed to determine the etiology of this disparity and highlights the need for targeted strategies to help at-risk patient populations.

The seeds of Nigella sativa Linn. (Ranunculaceae), commonly known as Black cumin, are predominantly used as carminative, antispasmodic, and stimulant. The main objective of the present study was to evaluate the effect of N. sativa seed extract on the permeation of co-infused amoxicillin across the gut wall. The methanolic extract of N. sativa improved intestinal permeability of amoxicillin in in-vitro experiments in a dose-dependent manner. Two new glycosides, decanyl nigelloic acid diglucoside [n-decanyl-3-aldehydic-4-methoxy-5-hydroxy benzoate-5-β-D-glucofuranosyl (2→1)-β-D-glucopyranosyl-(2→1)-β-D-glucopyranoside]] and nigelabdienoyl triglucoside [homo-labd-5, 9(11)-dien-16-onyl-β-D-glucopyranosyl (2→1)-β-D-glucopyranosyl (2→1)-β-D-glucopyranoside], along with seven known fatty acid glycerides/esters, were isolated from the gut permeation enhancing extract. The structures of these new glycosides were elucidated by detailed spectroscopic analyses.
Amoxicillin ; pharmacokinetics ; Animals ; Anti-Bacterial Agents ; pharmacokinetics ; Intestine, Small ; metabolism ; Male ; Molecular Structure ; Nigella sativa ; chemistry ; Phytochemicals ; chemistry ; metabolism ; Plant Extracts ; chemistry ; metabolism ; Rats ; Rats, Wistar ; Seeds ; chemistry

Objective To predict immunogenic promiscuous T cell epitopes from the polyprotein of the Zika virus using a range of bioinformatics tools. To date, no epitope data are available for the Zika virus in the IEDB database. Methods We retrieved nearly 54 full length polyprotein sequences of the Zika virus from the NCBI database belonging to different outbreaks. A consensus sequence was then used to predict the promiscuous T cell epitopes that bind MHC 1 and MHC II alleles using PorPred1 and ProPred immunoinformatic algorithms respectively. The antigenicity predicted score was also calculated for each predicted epitope using the VaxiJen 2.0 tool. Results By using ProPred1, 23 antigenic epitopes for HLA class I and 48 antigenic epitopes for HLA class II were predicted from the consensus polyprotein sequence of Zika virus. The greatest number of MHC class I binding epitopes were projected within the NS5 (21%), followed by Envelope (17%). For MHC class II, greatest number of predicted epitopes were in NS5 (19%) followed by the Envelope, NS1 and NS2 (17% each). A variety of epitopes with good binding affinity, promiscuity and antigenicity were predicted for both the HLA classes. Conclusion The predicted conserved promiscuous T-cell epitopes examined in this study were reported for the first time and will contribute to the imminent design of Zika virus vaccine candidates, which will be able to induce a broad range of immune responses in a heterogeneous HLA population. However, our results can be verified and employed in future efficacious vaccine formulations only after successful experimental studies.

Nowadays, use of alternative and complementary therapies with mainstream medicine has gained the momentum. Aromatherapy is one of the complementary therapies which use essential oils as the major therapeutic agents to treat several diseases. The essential or volatile oils are extracted from the flowers, barks, stem, leaves, roots, fruits and other parts of the plant by various methods. It came into existence after the scientists deciphered the antiseptic and skin permeability properties of essential oils. Inhalation, local application and baths are the major methods used in aromatherapy that utilize these oils to penetrate the human skin surface with marked aura. Once the oils are in the system, they remodulate themselves and work in a friendly manner at the site of malfunction or at the affected area. This type of therapy utilizes various permutation and combinations to get relief from numerous ailments like depression, indigestion, headache, insomnia, muscular pain, respiratory problems, skin ailments, swollen joints, urine associated complications etc. The essential oils are found to be more beneficial when other aspects of life and diet are given due consideration. This review explores the information available in the literature regarding therapeutic, medical, cosmetic, psychological, olfactory, massage aromatherapy, safety issues and different plants used in aromatherapy. All the available information was compiled from electronic databases such as Academic Journals, Ethnobotany, Google Scholar, PubMed, Science Direct, Web of Science, and library search.