Notes

Management of musculoskeletal tumours with the extremity inside low-resource options.
Breast cancer is caused by abnormal growth of the cells and progressed due to the over-expression of estrogen (ER) and progesterone (PR). The current study was designed to evaluate the anti-tumor activity of 2,4,6 tris-methyphenylamino1,3,5-triazine compound (MPAT) in N-nitroso, N-methyl urea (NMU)-induced mammary gland cancer.

Molecular docking and in-vitro studies were conducted before the in-vivo analysis. Female Albino rats were divided into 5 groups (n=6). Group I received Carboxymethylcellulose (CMC) (1mL/100g). Group II (diseased group) received NMU 50mg/kg. Group III (standard group) received tamoxifen (5mg/kg). Group IV-V received MPAT at doses of 30 and 60mg/kg respectively. All groups received NMU intraperitoneally except the control group at 3weeks intervals for 12weeks. After 12weeks of NMU dosing, MPAT was given for 15 consecutive days. Biochemical, oxidative stress markers, hormonal profile, and inflammatory mediators were analyzed.

MPAT showed significant interaction with the selected targets in docking studies. An over-expression of ER and PR was observed in NMU-treated rats which were restored significantly after MPAT administration. Nitrite and MDA levels were high in the diseased group and MPAT treatment attenuated the oxidative damage after treatment. Antioxidants such as superoxide dismutase (SOD), Catalase (CAT), total sulfhydryl (TSH), glutathione (GSH), and Lactate dehydrogenase (LDH) values were low in NMU-treated rats.

This study concluded that MPAT can be used as an anticancer agent due to its significant effects on down-regulating the hormonal profile and oxidative stress markers.
This study concluded that MPAT can be used as an anticancer agent due to its significant effects on down-regulating the hormonal profile and oxidative stress markers.Terbutaline sulphate (TS) is a selective short-acting β2 adrenoceptor agonist used for asthma treatment. The pharmacological activity of TS depends on its binding to the transmembrane protein, β2 adrenoceptor. Thus, the interactions of this drug with biological membranes are expected, affecting its pharmacological activity. Using in vitro models to study the interaction of TS with biological membranes can provide important information about the activity of the drug. Here, liposomes with different lipid compositions were used as biomimetic models of cell membranes to evaluate the effect of composition, complexity, and physical state of membranes on TS-membrane interactions. For that, liposomes containing dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and liposomes containing DMPC and cholesterol (CHOL) were prepared. For the study of TS-membrane interactions, the TS lipophilicity was evaluated in terms of i) partition coefficient; ii) the preferential location of the drug within the membrane; iii) and the effect of TS on the membrane fluidity. The obtained data suggest that TS has an affinity for the lipid membrane, partitioning from the aqueous to the lipid phase. The affinity was dependent on the liposomes' compositions, showing a greater affinity for DMPC membranes than for DMPCCHOL model. Dynamic light scattering (DLS) results revealed that this is due to the rigidizing effect caused by CHOL molecules. These findings provide valuable insights in the understanding of the complex interaction of TS with biomembrane models as well as the relevance of lipid compositions and membrane structure in such interactions, which may be related to its pharmacological activity and side effects.Berberine, an isoquinoline alkaloid, is reported for the treatment of Alzheimer's disease. Despite having substantial therapeutic potential, it exhibits poor absorption, low oral bioavailability and limited penetration in the brain. In this study, berberine-loaded nanostructured lipid carriers (Berb-NLCs) were developed by melt-emulsification and ultrasonication using Geleol, Miglyol 812 N, Solutol HS 15 as a solid lipid, liquid lipid and surfactant, respectively. The Berb-NLC formulation was statistically optimized by a 32 factorial design in which the effect of surfactant and berberine concentration was assessed on particle size and entrapment efficiency of Berb-NLCs. Optimized Berb-NLCs (Trial-5) exhibited particle size of 186 nm, polydispersity index of 0.108, the zeta potential of -36.86 mV and 88% entrapment efficiency. The in vitro release of berberine from Batch-B5 was 82% in phosphate buffer at the end of 24 h. The comparative results of pharmacodynamic studies involving behavioral assessment by locomotor activity, passive avoidance test, elevated plus maze test and spatial memory assessment by Morris water maze demonstrated improved behavioral parameters in vivo by Berb-NLCs compared to pure berberine in Albino Wistar rats. Thus, berberine-loaded nanostructured lipid carriers have the potential of brain targeting and were effective in an animal model of Alzheimer's disease.
Hepatic ischemia reperfusion injury (HIRI) is a complication of liver surgery and liver transplantation. Adipose-derived stem cells (ADSCs) can inhibit oxidative stress and inflammation through a paracrine effect. This study aimed to determine the optimal time window of ADSCs transplantation to restore liver function after HIRI.

A rat model of hepatic ischemia reperfusion combined with partial hepatectomy (HIR/PH) was established. The animals were injected intravenously with 2×10
rat ADSCs 2h before, immediately after, or 6h after surgery. Liver tissues and blood samples were collected for routine histological and biochemical assays. The molecular changes were analyzed by qRT-PCR and western blotting.

ADSCs significantly improved liver tissue structure and decreased the levels of AST, ALT and ALP, which was indicative of functional recovery. In addition, transplantation of ADSCs immediately after operation decreased the levels of inflammation-related cytokines such as TNF-α, IL-1β and IL-6, and significantly increased the activity of antioxidant enzymes. At the same time, the expression of MDA was decreased. Mechanistically, ADSCs activated the Keap1/Nrf2 pathway in the injured liver. Transplantation of ADSCs pre- and 6h post-operation did not significantly affect some indices such as mRNA and protein expression of HO-1, and protein expression of NQO1.

Transplanting ADSCs immediately after surgery accelerated tissue repair and functional recovery of the liver by activating the Keap1/Nrf2 pathway, which inhibited hepatic inflammation and oxidative stress, and restored the hepatic microenvironment.
Transplanting ADSCs immediately after surgery accelerated tissue repair and functional recovery of the liver by activating the Keap1/Nrf2 pathway, which inhibited hepatic inflammation and oxidative stress, and restored the hepatic microenvironment.
Diabetes, a serious worldwide problem, is modulated via inflammation and oxidative stress. Bromelain, a natural compound, recently attracts interest due to its anti-inflammatory effects, while its mode of action remains not properly understood. Thus, investigating the antidiabetic effect of bromelain is promising.

Rats were randomized into normal group, STZ group (were administrated single intraperitoneal (i.p) injection of 55mg/kg streptozotocin (STZ)) and STZ+Bro group (were administrated single i.p injection of STZ, 72h later were i.p administrated 10mg/kg/day bromelain for 15days). Wound healing ability was investigated for different groups. Spectrophotometry, ELISA, histopathological and immunohistochemical techniques were applied.

Bromelain significantly decreased fasting blood glucose, serum triglycerides and cholesterol and hepatic malondialdehyde levels compared with STZ group. U0126 Moreover, Bromelain significantly increased serum albumin and total protein levels and percentage of wound healing comelain in STZ-induced diabetes in rats.
Characterizing cannabinoid receptors (CBRs) expressed in Ewing sarcoma (EWS) cell lines as potential targets for anti-cancer drug development.

CBR affinity and function were examined by competitive binding and G-protein activation, respectively. Cannabinoid-mediated cytotoxicity and cell viability were evaluated by LDH, and trypan blue assays, respectively.

qRT-PCR detected CB1 (CB1R) and CB2 receptor (CB2R) mRNA in TC-71 cells. However, binding screens revealed that CBRs expressed exhibit atypical properties relative to canonical receptors, because specific binding in TC-71 could only be demonstrated by the established non-selective CB1/CB2R radioligand [
H]WIN-55,212-2, but not CB1/CB2R radioligand [
H]CP-55,940. Homologous receptor binding demonstrated that [
H]WIN-55,212-2 binds to a single site with nanomolar affinity, expressed at high density. Further support for non-canonical CBRs expression is provided by subsequent binding screens, revealing that only 9 out of 28 well-characterized cannabinoids with high affinity for canonical CB1 and/or CB2Rs were able to displace [
H]WIN-55,212-2, whereas two ligands enhanced [
H]WIN-55,212-2 binding. Five cannabinoids producing the greatest [
H]WIN-55,212-2 displacement exhibited high nanomolar affinity (K
) for expressed receptors. G-protein modulation and adenylyl cyclase assays further indicate that these CBRs exhibit distinct signaling/functional profiles compared to canonical CBRs. Importantly, cannabinoids with the highest affinity for non-canonical CBRs reduced TC-71 viability and induced cytotoxicity in a time-dependent manner. Studies in a second EWS cell line (A-673) showed similar atypical binding properties of expressed CBRs, and cannabinoid treatment produced cytotoxicity.

Cannabinoids induce cytotoxicity in EWS cell lines via non-canonical CBRs, which might be a potential therapeutic target to treat EWS.
Cannabinoids induce cytotoxicity in EWS cell lines via non-canonical CBRs, which might be a potential therapeutic target to treat EWS.
Elevated Treg is relevant to persistent HBV infection, and the regulatory mechanism of Treg levels remains unclear. E proteins are important transcriptional regulators and could be antagonized by inhibitors of DNA-binding (Id) 1-4. We aim to clarify the role of Ids during HBV infection.

Changes of Ids and their relationship with Treg were investigated in both HBV transfection model and hepatitis B patients. Significance of Ids was studied by in vitro Treg differentiation induction with Id inhibited or over-expressed. The role of inflammatory cytokines for Id was studied by co-culture. RNA-Seq was conducted to explore the differentially expressed genes in Id-overexpressed CD4 T cells upon Treg differentiation induction conditions.

Id-overexpressed mice attenuated virus clearance in HBV transfection model. In the HBV transfection mouse model, Tregs were up-regulated, with Id3 increased in Treg as well. Clinically, circulating Tregs in chronic hepatitis B (CHB) patients were elevated, and elevated Id3 transcriptional levels were positively correlated with Tregs. IL-1β could up-regulate Id3 in Treg cells induced in vitro. RNA-Seq revealed that increased Id could cause a series of signaling pathway changes during Treg differentiation.

Id3 is elevated during HBV infection to ease Treg differentiation, and the antiviral immunity is influenced that make the infection to develop into chronic state.
Id3 is elevated during HBV infection to ease Treg differentiation, and the antiviral immunity is influenced that make the infection to develop into chronic state.
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