Cell membrane-coated biomimetic nanomedicines: productive cancer theranostic tools.

As the second-leading cause of human death, cancer has drawn attention in the area of biomedical research and therapy from all around the world. Certainly, the development of nanotechnology has made it possible for nanoparticles (NPs) to be used as a carrier for delivery systems in the treatment of tumors. This is a biomimetic approach established to craft remedial strategies comprising NPs cloaked with membrane obtained from various natural cells like blood cells, bacterial cells, cancer cells, etc. Here we conduct an in-depth exploration of cell membrane-coated NPs (CMNPs) and their extensive array of applications including drug delivery, vaccination, phototherapy, immunotherapy, MRI imaging, PET imaging, multimodal imaging, gene therapy and a combination of photothermal and chemotherapy. This review article provides a thorough summary of the most recent developments in the use of CMNPs for the diagnosis and treatment of cancer. It critically assesses the state of research while recognizing significant accomplishments and innovations. Additionally, it indicates ongoing problems in clinical translation and associated queries that warrant deeper research. By doing so, this study encourages creative thinking for future projects in the field of tumor therapy using CMNPs while also educating academics on the present status of CMNP research.

Polyherbal extract improves glycometabolic control in alloxan-induced diabetic rats via down-regulating the MAPK/JNK pathway, modulating Nrf-2/Keap-1 expression, and stimulating insulin signaling.

Objectives: This study focused on the evaluation of antioxidant and antidiabetic activities of polyherbal extract (PHE), containing Cassia absus (L.), Gymnema sylvestre (R. Br.), Nigella sativa (L.), and Piper nigrum (L.), in alloxan-induced diabetes model. Materials and Methods: In vitro, HPLC characterization, DPPH scavenging assay, and α-amylase inhibition test were conducted. In vivo, acute oral toxicity of PHE was assessed. Alloxan-induced diabetic Wistar rats (n=6) were orally treated with PHE (200, 400, and 600 mg/kg/day) and glibenclamide (GLB; 10 mg/kg/day) for six consecutive weeks. Then, biochemical biomarkers, oxidative stress parameters, histopathological examination, and mRNA expression levels (RT-qPCR) were determined. Results: The presence of polyphenols in PHE was confirmed in correlation to marked DPPH scavenging (IC50: 1.60 mg/ml) and α-amylase inhibition (IC50: 0.82 mg/ml). PHE demonstrated no toxicity in rats up to a dose of 2000 mg/kg. In diabetic rats, PHE dose-dependently ameliorated the serum levels of glucose, insulin, glycated hemoglobin A1c (HbA1c), leptin, and glucokinase (GCK). Also, PHE substantially alleviated serum inflammatory markers (TNF-α and CRP) and oxidative stress indicators (MDA, SOD, and CAT) in pancreatic tissues. PHE, particularly at 600 mg/kg, attenuated cellular oxidative stress via modulating the mRNA expression levels of genes regulating MAPK/JNK (Mapk-8, Traf-4, and Traf-6) and Nrf-2/Keap-1 pathways and promoted insulin signaling through up-regulating insulin signaling cascade (Pdx-1, Ins-1, and Ins-2), as compared to GLB. Furthermore, histopathological findings supported the aforementioned results. Conclusion: Our study suggests that polyherbal extract has promising antioxidant and antidiabetic activities by modulating the MAPK/JNK, Nrf-2/Keap-1, and insulin signaling pathways.

In vitro Antioxidant Activity and In vivo Anti-inflammatory Effect of Ricinus communis (L.) and Withania somnifera (L.) Hydroalcoholic Extracts in Rats

Abstract Ricinus communis L. and Withania somnifera L. have traditionally been used as analgesic and anti-inflammatory remedies. The current study was aimed to evaluate the in vitro antioxidant potential and anti-inflammatory activity of hydroalcoholic extract of R. communis leaves (RCE) and W. somnifera roots (WSE) in Wistar rats. Total phenolic and flavonoid contents were quantified and in vitro antioxidant activity of extracts was determined through DPPH* scavenging, superoxide anion scavenging and reducing power activities, while anti-inflammatory activity was observed by xylene-induced ear edema and paw edema induced by egg albumin and carrageenan. RCE and WSE demonstrated considerable antioxidant activity in DPPH* scavenging (IC50: 250.10 and 309.42 µg/mL), superoxide anion scavenging (IC50: 193.42 and 206.81 ug/mL), and reducing power (maximum absorbance: 1.47±0.01 O.D and 1.28±0.01 O.D at 500 ug/mL) activities, respectively, with high phenolic and flavonoid contents. Both extracts showed dose-dependent edema inhibition in inflammation models. A maximum ear edema inhibitions by RCE (51.49±2.54%) and WSE (49.28±1.90%) at 500 mg/kg were observed when compared to indomethacin (56.42±13.17%) in xylene-induced ear edema. RCE and WSE showed a maximum percentage of paw edema inhibitions of 46.62±8.98% and 43.00±12.44%, respectively as compared to chlorpheniramine (62.02±12.21%) after 4 h in the egg albumin model. In carrageenan-induced paw edema, RCE (72.88±13.79%) significantly inhibited paw edema in comparison to WSE (57.81±17.43%) against diclofenac (89.93±18.53%). Conclusively, both plants have shown plausible antioxidant and anti-inflammatory activities that might be due to high phenolic and flavonoid contents. Moreover, RCE demonstrated more promising effects than WSE.

Quorum Sensing Interfering Strategies and Their Implications in the Management of Biofilm-Associated Bacterial Infections

Abstract The bacterial species employ various types of molecular communication systems recognized as quorum sensing for the synchronization of differential gene expression to regulate virulence traits and biofilm formation. A variety of quorum sensing inhibitors; molecules that interfere with quorum sensing among bacteria have been examined which can block the action of autoinducers. Moreover, the studies have scrutinized various enzymes for their quorum quenching activity resulting in the degradation of signaling molecules or blocking of gene expression. So far, the studies have found that these approaches are not only capable to reduce the pathogenicity and biofilm formation but also resulted in increased bacterial susceptibility to antibiotics and bacteriophages. The effectiveness of these strategies has been validated in different animal models and it seems that these practices will be transformed in near future to develop the medical devices including catheters, implants, and dressings for the prevention of bacterial infections. Although many of these approaches are still in the research stage, the increasing library of quorum quenching molecules and enzymes will open innovative perspectives for the development of antibacterial approaches which will extend the therapeutic arsenal against the pathogenic bacterial species.

Antimicrobial susceptibility of acinetobacter clinical isolates and emerging antibiogram trends for nosocomial infection management

Abstract: Introduction: The drug resistant Acinetobacter strains are important causes of nosocomial infections that are difficult to control and treat. This study aimed to determine the antimicrobial susceptibility patterns of Acinetobacter strains isolated from different clinical specimens obtained from patients belonging to different age groups. METHODS: In total, 716 non-duplicate Acinetobacter isolates were collected from the infected patients admitted to tertiary-care hospitals at Lahore, Pakistan, over a period of 28 months. The Acinetobacter isolates were identified using API 20E, and antimicrobial susceptibility testing was performed and interpreted according to Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: The isolation rate of Acinetobacter was high from the respiratory specimens, followed by wound samples. Antibiotic susceptibility analyses of the isolates revealed that the resistance to cefotaxime and ceftazidime was the most common, in 710 (99.2%) specimens each, followed by the resistance to gentamicin in 670 (93.6%) isolates, and to imipenem in 651 (90.9%) isolates. However, almost all isolates were susceptible to tigecycline, colistin, and polymyxin B. CONCLUSIONS: The present study showed the alarming trends of resistance of Acinetobacter strains isolated from clinical specimens to the various classes of antimicrobials. The improvement of microbiological techniques for earlier and more accurate identification of bacteria is necessary for the selection of appropriate treatments.