Activity

Curcuma longa Linn. (C. longa), popularly known as turmeric, belongs to the Zingiberaceae family and has a long historical background of having healing properties against many diseases. In Unani and Ayurveda medicine, C. longa has been used for liver obstruction and jaundice, and has been applied externally for ulcers and inflammation. Additionally, it is employed in several other ailments such as cough, cold, dental issues, indigestion, skin infections, blood purification, asthma, piles, bronchitis, tumor, wounds, and hepatic disorders, and is used as an antiseptic. Curcumin, a major constituent of C. longa, is well known for its therapeutic potential in numerous disorders. However, there is a lack of literature on the therapeutic potential of C. longa in contrast to curcumin. Hence, the present review aimed to provide in-depth information by highlighting knowledge gaps in traditional and scientific evidence about C. longa in relation to curcumin. The relationship to one another in terms of biological action includes their antioxidant, anti-inflammatory, neuroprotective, anticancer, hepatoprotective, cardioprotective, immunomodulatory, antifertility, antimicrobial, antiallergic, antidermatophytic, and antidepressant properties. Furthermore, in-depth discussion of C. longa on its taxonomic categorization, traditional uses, botanical description, phytochemical ingredients, pharmacology, toxicity, and safety aspects in relation to its major compound curcumin is needed to explore the trends and perspectives for future research. Considering all of the promising evidence to date, there is still a lack of supportive evidence especially from clinical trials on the adjunct use of C. longa and curcumin. This prompts further preclinical and clinical investigations on curcumin.Glioblastoma multiforme (GBM) is the most common as well as one of the most malignant types of brain cancer. Despite progress in development of novel therapies for the treatment of GBM, it remains largely incurable with a poor prognosis and a very low life expectancy. Recent studies have shown that oleandrin, a unique cardiac glycoside from Nerium oleander, as well as a defined extract (PBI-05204) that contains this molecule, inhibit growth of human glioblastoma, and modulate glioblastoma patient-derived stem cell-renewal properties. Here we demonstrate that PBI-05204 treatment leads to an increase in vitro in the sensitivity of GBM cells to radiation in which the main mechanisms are the transition from autophagy to apoptosis, enhanced DNA damage and reduced DNA repair after radiotherapy (RT) administration. The combination of PBI-05204 with RT was associated with reduced tumor progression evidenced by both subcutaneous as well as orthotopic implanted GBM tumors. Collectively, these results reveal that PBI-05204 enhances antitumor activity of RT in preclinical/murine models of human GBM. Given the fact that PBI-05204 has already been examined in Phase I and II clinical trials for cancer patients, its efficacy when combined with standard-of-care radiotherapy regimens in GBM should be explored.Oxytocin (OT) and its receptor are promising targets for the treatment and prevention of the neuropathic pain. In the present study, we compared the effects of a single and continuous intrathecal infusion of OT on nerve injury-induced neuropathic pain behaviours in mice and further explore the mechanisms underlying their analgesic properties. We found that three days of continuous intrathecal OT infusion alleviated subsequent pain behaviours for 14 days, whereas a single OT injection induced a transient analgesia for 30 min, suggesting that only continuous intrathecal OT attenuated the establishment and development of neuropathic pain behaviours. Supporting this behavioural finding, continuous intrathecal infusion, but not short-term incubation of OT, reversed the nerve injury-induced depolarizing shift in Cl- reversal potential via restoring the function and expression of spinal K+-Cl- cotransporter 2 (KCC2), which may be caused by OT-induced enhancement of GABA inhibitory transmission. This result suggests that only continuous use of OT may reverse the pathological changes caused by nerve injury, thereby mechanistically blocking the establishment and development of pain. selleck chemical These findings provide novel evidence relevant for advancing understanding of the effects of continuous OT administration on the pathophysiology of pain.Chaenomeles speciosa (Sweet) Nakai has been long used as a folk medicine for rheumatic diseases treatment. This study aimed to investigate the effects and underlying mechanism of polysaccharides in Chaenomeles speciosa (CSP) on the pro-inflammatory cytokines and MAPK pathway in complete Freund’s adjuvant (CFA)-induced arthritis and LPS-induced NR8383 cells. We used acetic acid (HAc)-induced writhing and CFA induced paw edema to determine the analgesic activity and anti-inflammatory activity, respectively. CFA rats were administered CSP (12.5, 25.0, and 50.0 mg/kg) daily for 3 weeks via oral gavage. The analgesic test was done using three different doses of the extract (50, 100, and 200 mg/kg). The anti-arthritic evaluation involved testing for paw swelling, swelling inhibition, and histological analysis in CFA rats. Finally, ELISA, western blot, qRT-PCR were done to determine the effect of CSP on the activation of MAPK pathway, production of pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated NR838 macrophage cells. In pain models, oral uptake of CSP greatly reduced pain perception. Furthermore, in CFA rats, CSP substantially decreased paw swelling as well as synovial tissue proliferation and inflammatory cell infiltration. In addition, CSP was shown to inhibit pro-inflammatory cytokines (TNF-α, IL-1β, and COX-2) as well as JNK and ERK1/2 phosphorylation in LPS-stimulated NR8383 cells. Thus, pro-inflammatory cytokine secretion and MAPK signaling downregulation promoted the analgesic and anti-arthritic effects of CSP.The plasma membrane transporter LAT1 (SLC7A5) is a crucial player for cell homeostasis because it is responsible for providing cells with essential amino acids and hormones. LAT1 forms a functional heterodimer with the cell surface antigen heavy chain CD98 (also known as 4F2hc and SLC3A2), a type II membrane glycoprotein, which is essential for LAT1 stability and localization to the plasma membrane. The relevance of LAT1 for human metabolism is also related to its altered expression in human diseases, such as cancer and diabetes. These features boosted research toward molecules that are able to interact with LAT1; in this respect, the recent resolution of the LAT1-CD98 3D structure by Cryo-EM has opened important perspectives in the study of the interaction with different molecules in order to identify new drugs to be used in therapy or new substrates of natural origin to be employed as adjuvants and food supplements. In this work, the interaction of LAT1 with alliin, a garlic derivative, has been investigated by using a combined approach of bioinformatics and in vitro transport assays. Alliin is a nutraceutical that has several beneficial effects on human health, such as antidiabetic, anticarcinogenic, antioxidant, and anti-inflammatory properties. The computational analysis suggested that alliin interacts with the substrate binding site of LAT1, to which alliin was docked. These data were then confirmed by the competitive type inhibition measured in proteoliposomes. Interestingly, in the same experimental model, alliin was also revealed to be a substrate of LAT1.Background Immune checkpoint inhibitors (ICIs) have become an effective treatment option for cancer. KRAS, EGFR and TP53 are common mutated oncogenes in cancer whose single gene status may predict the therapeutic effect of clinical ICIs. In this efficacy evaluation, we aimed to clarify whether the single gene mutation status of KRAS, EGFR or TP53 affects the survival benefits of ICIs in cancer patients. Methods We used PubMed, Cochrane Library, web of science, and clinical trials Gov database to retrieve qualified documents, the time was up to January 2022. Hazard ratios (HRS) and 95% confidence intervals (CIs) were used to determine the single gene mutation status and no progression of KRAS, EGFR or TP53. Results A total of 19 studies included 7029 cancer patients treated with ICIs. The results showed that KRAS, EGFR or TP53 single gene mutation could significantly improve PFS and OS in patients receiving ICIs, but the degree of improvement was different. The risk of prolongation of PFS (HR = 1.48, 95% CI = 1.19-1.85, p = 0.0004) and OS (HR = 1.68, 95% CI = 1.36-2.07, p less then 0.00001) caused by TP53 single gene mutation was relatively high, the risk ratio of prolongation of PFS (HR = 1.38, 95% CI = 1.21-1.57, p less then 0.00001) and OS (HR = 1.56, 95% CI = 1.20-2.04, p = 0.001) caused by EGFR single gene mutation was the second, the risk ratio of prolongation of PFS (HR = 1.33, 95% CI = 1.12-1.57, p = 0.001) and OS (HR = 1.39, 95% CI = 1.18-1.63, p less then 0.00001) caused by KRAS single gene mutation was relatively low, and the results were significantly different. Conclusion In cancer patients, KRAS, EGFR or TP53 single gene status is correlated with the benefits of immunotherapy PFS and OS, which suggests that gene sequencing should be carried out in time in the process of clinical treatment to determine the gene mutation of patients and better predict the clinical treatment effect of ICIs.Tumor hypoxic microenvironment can reduce the therapeutic effects of chemotherapy, radiotherapy, photodynamic therapy, immunotherapy, etc. It is also a potential source of tumor recurrence and metastasis. A biomimetic nanosystem based on zeolitic imidazolate framework 8 (ZIF8), which had multifunctions of hypoxia relief, chemotherapy, and photothermal therapy, was established to improve tumor hypoxic microenvironment and overcome the corresponding therapeutic resistance. ZIF8 enveloped with DOX and CuS nanoparticles (DC@ZIF8) was synthesized by a sedimentation method. Red blood cell membrane and catalase (CAT) were coated onto DC@ZIF8 and biomimetic nanosystem (DC@ZIF8-MEMC) was formed. The designed DC@ZIF8-MEMC had a shape of polyhedron with an average particle size around 254 nm. The loading content of DOX, CAT, and CuS was 4.9%, 6.2%, and 2.5%, separately. The release of DOX from DC@ZIF8-MEMC was pH dependent and significantly faster at pH 5 due to the degradation of ZIF8. DC@ZIF8-MEMC exhibited outstanding photothermal conversion properties and excellent antitumor effect in vitro and in vivo. Moreover, the hypoxia relief by CAT was proved to have good sensitization effect on chemo-photothermal combined therapy. DC@ZIF8-MEMC is a prospective nanosystem, which can realize great chemo-photothermal synergistic antitumor effect under the sensitization of CAT. The biomimetic multifunctional nanoplatform provides a potential strategy of chemo-photothermal synergistic antitumor effect under the sensitization of CAT.Due to the fast mutating nature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the development of novel therapeutics, vaccines, and evaluating the efficacies of existing one’s against the mutated strains is critical for containing the virus. Pseudotyped SARS-CoV-2 viruses are proven to be instrumental in evaluating the efficiencies of therapeutics, owing to their ease in application and safety when compared to handling the live virus. However, a comprehensive protocol that includes selecting transfection reagents, validating different packaging systems for high-throughput screening of neutralizing antibodies, is still a requisite. To this end, we designed and synthesized amide linker-based cationic lipids with varying hydrophilic head groups from dimethyl (Lipo-DME) to methyl, ethylhydroxyl (Lipo-MeOH), and diethylhydroxyl (Lipo-DOH) keeping the hydrophobic tail, stearic acid, as constant. Among the liposomal formulations of these lipids, Lipo-DOH was found to be superior in delivering plasmids and demonstrated comparable transfection efficiencies with commercial standard Lipofectamine 3000.