Notes

Effects of ectomycorrhizal infection bolete personality on the local community assemblages regarding endofungal germs.
With the introduction of antiretroviral therapy, the worldwide AIDS-related deaths have decreased, and life expectancy has increased, so has the prevalence of AIDS-related neurological disorders or neuroAIDS. HIV associated neurocognitive disorder such as mild neurocognitive disorder and asymptomatic neurocognitive impairment have largely remained stable or increased among the HIV infected individuals in the combination antiretroviral therapy era and with the emerging evidence that antiretrovirals with high CNS penetration effectiveness score contribute to the neurotoxicity and HIV associated neurocognitive disorder. read more have ushered the search for natural, nontoxic bioactive constituents having pre-established neuroprotective, anti-inflammatory and restorative neurocognitive activity. In this review, we have highlighted the probable mechanism of neuroAIDS infection, the problem with the existing antiretroviral therapy, along with various bioactive constituents with in vivo, in vitro, or ex vivo evidence of their neuroprotective activity that can be used as an adjuvant with the current combination antiretroviral therapy regimen or can even serve as an alternate to the antiretrovirals for treatment of HIV associated neurocognitive disorder.Cancer notably carcinoma represents a prominent health challenge worldwide. A variety of chemotherapeutic agents are being used to deal with a variety of carcinomas. However, these delivering agents not only enter the targeted site but also affect normal tissues yielding poor therapeutic outcomes. Chemotherapeutic-associated problems are been attributed to drug non-specificity resulting from poor drug delivery systems. These problems are now been solved using nanomedicine which entails using nanoparticles as drug delivery systems or nanocarriers. This nanoparticle-based drug delivery system enhances clinical outcomes by enabling targeted delivery, improving drug internalization, enhanced permeability, easy biodistribution, prolonged circulation and enhanced permeability rate thereby improving therapeutic effectiveness of several anticancer agents. Natural protein-based nanoparticles (PNPs) such as ferritin, lipoprotein, and lectins from natural sources have gained extensive importance at scientific community level as nanovehicle for effective drug delivery and photo acoustic labeling replacing several synthetic nanocarriers that have shown limited therapeutic outcomes. The bioavailability of PNP, chance of genetic engineering techniques to modify their biological properties made them one of the important raw material sources for drug delivery research. This current review highlighted different chemotherapeutic agents used in the treatment of some carcinomas. It also focused on the wide variety of natural protein sources derived nanoparticles (NPs) as anticancer delivery of agents for cancer therapy.
NONO-TFE3 translocation renal cell carcinoma (tRCC), one of RCCs associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 tRCCs), involves an X chromosome inversion between NONO and TFE3 with the characteristics of endonuclear aggregation of NONO-TFE3 fusion protein. Nowadays, the oncogenic mechanisms of NONO-TFE3 fusion have not been fully elucidated.

This study aimed at investigating the mechanism of NONO-TFE3 fusion regulating HIF1A as well as the role of HIF-1α in the progression of NONO-TFE3 tRCC under hypoxia.

Immunohistochemistry and Western Blotting assays were performed to profile HIF-1α expression in renal clear cell carcinoma (ccRCC) or in Xp11.2 tRCC. Chromatin immunoprecipitation (ChIP), luciferase reporter assay and real-time quantitative PCR (RT-qPCR) were used to evaluate the regulation of HIF1A expression by NONO-TFE3 fusion. Then, flow cytometry analysis, tube formation assays and cell migration assays were used as well as glucose or lactic acid levels were measured to establish the impact of HIF-1α on the progression of NONO-TFE3 tRCC. Besides, the effect of HIF-1α inhibitor (PX-478) on UOK109 cells was analyzed.

We found that HIF1A was targeting gene of NONO-TFE3 fusion. In UOK109 cells, which were isolated from NONO-TFE3 tRCC samples, NONO-TFE3 fusion promoted aerobic glycolysis and angiogenesis by up-regulating the expression of HIF-1α under hypoxia. Furthermore, inhibition of HIF-1α mediated by PX-478 suppressed the development of NONO-TFE3 tRCC under hypoxia.

HIF-1α is a potential target for therapy of NONO-TFE3 tRCC under hypoxia.
HIF-1α is a potential target for therapy of NONO-TFE3 tRCC under hypoxia.
Folate-conjugated Pluronic F87-poly(lactic-co-glycolic acid) block copolymer (FA-F87-PLGA) was synthesized to encapsulate anticancer drug Paclitaxel (PTX) for targeted drug delivery. To further improve the curative effect, D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS or Vitamin E TPGS) was added to form FA-F87-PLGA/TPGS mixed NPs.

FA-F87-PLGA was synthesized by the ring-opening polymerization and the structure was characterized. PTX-loaded nanoparticles were prepared with the nanoprecipitation method. The physicochemical characteristics were studied to determine the appropriate dose ratio of the FA-F87-PLGA to TPGS. The cytotoxicity against Ovarian Cancer Cells (OVCAR-3) was determined by MTT assay. The Area-Under-the Curve (AUC) and half-life were measured in the vivo pharmacokinetic studies.

Based on the optimization of particle size and embedding rate of PTX-loaded mixed NPs, the appropriate dosage ratio of FA-F87-PLGA to TPGS was finally determined to be 53. According to in vitro release studies, the cumulative release rate of PTX-loaded FA-F87-PLGA/TPGS mixed NPs was 92.04%, which was higher than that of nanoparticles without TPGS. The cytotoxicity studies showed that the IC50 value of PTX-loaded FA-F87-PLGA/TPGS decreased by 75.4 times and 19.7 times after 72 h treatment compared with free PTX injections and PTX-loaded FA-F87-PLGA NPs, respectively. In vivo pharmacokinetic studies indicated that FA-F87-PLGA/TPGS mixed NPs had a longer drug metabolism time and a larger Area-Under-the-Curve (AUC) compared with free PTX injections.

FA-F87-PLGA/TPGS mixed NPs are potential candidates for targeted drug delivery systems.
FA-F87-PLGA/TPGS mixed NPs are potential candidates for targeted drug delivery systems.
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