Neutralizing tumor-related inflammation and reprogramming of cancer-associated fibroblasts by Curcumin in breast cancer therapy.

Tumor-associated inflammation plays a vital role in cancer progression. Among the various stromal cells, cancer-associated fibroblasts are promising targets for cancer therapy. Several reports have indicated potent anti-inflammatory effects attributed to Curcumin. This study aimed to investigate whether inhibiting the inflammatory function of cancer-associated fibroblasts (CAFs) with Curcumin can restore anticancer immune responses. CAFs were isolated from breast cancer tissues, treated with Curcumin, and co-cultured with patients' PBMCs to evaluate gene expression and cytokine production alterations. Blood and breast tumor tissue samples were obtained from 12 breast cancer patients with stage II/III invasive ductal carcinoma. Fibroblast Activation Protein (FAP) + CAFs were extracted from tumor tissue, treated with 10 µM Curcumin, and co-cultured with corresponding PBMCs. The expression of smooth muscle actin-alpha (α-SMA), Cyclooxygenase-2(COX-2), production of PGE2, and immune cell cytokines were evaluated using Real-Time PCR and ELISA, respectively. Analyzes showed that treatment with Curcumin decreased the expression of genes α-SMA and COX-2 and the production of PGE2 in CAFs. In PBMCs co-cultured with Curcumin-treated CAFs, the expression of FoxP3 decreased along with the production of TGF-ß, IL-10, and IL-4. An increase in IFN-γ production was observed that followed by increased T-bet expression. According to our results, Curcumin could reprogram the pro-tumor phenotype of CAFs and increase the anti-tumor phenotype in PBMCs. Thus, CAFs, as a component of the tumor microenvironment, are a suitable target for combination immunotherapies of breast cancer.

Consumption of pistachio nuts positively affects lipid profiles: A systematic review and meta-analysis of randomized controlled trials.

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of consuming pistachio nuts on lipid profiles (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglyceride [TG]). Databases of PubMed, Scopus, ISI Web of Science, and Cochrane Library were searched from inception to June 2019 to identify RCTs documenting the effects of consuming pistachio nuts on blood lipid profiles in adults. Effect sizes were reported as weighted mean difference (WMD) and 95% confidence interval (CI) using the random-effects models (DerSimonian-Laird method). Twelve eligible RCTs were included. Consumption of pistachio nuts decreased TC (WMD: -7.48 mg/dL; 95% CI, -12.62 to -2.34), LDL-C (WMD: -3.82 mg/dL; 95% CI, -5.49 to -2.16) and TG (WMD: -11.19 mg/dL; 95% CI, -14.21 to -8.17) levels. However, HDL-cholesterol levels (WMD: 2.45 mg/dL; 95% CI, -2.44 to 7.33) did not change following pistachio consumption. Consuming pistachio nuts may improve lipid profiles (TC, LDL-C, TG) in adults and may be protective against cardiometabolic diseases. However, further studies with larger sample sizes are required to confirm these results.

The role of NLRP3 inflammasome in colorectal cancer: potential therapeutic target

All phases of carcinogenesis are affected by inflammation. Activation of the inflammasome is a crucial signaling mechanism that leads to acute and chronic inflammation. When specific nucleotide-binding domains, leucine-rich repeat-containing proteins (NLRs) are activated, inflammasomes are formed. The NLRP3 is one of the NLR family members with the most functional characterization. NLRP3 can modulate the immune systems, apoptosis, growth, and/or the gut microbiome to impact cancer development. Colorectal cancer (CRC) is one of the most common cancers, and it begins as a tissue overgrowth on the internal part of the rectum or colon. In vivo and in vitro studies showed that the NLRP3 inflammasome has a role in CRC development due to its broad activity in shaping immune responses. Here, onwards, we focus on the NLRP3 inflammasome role in CRC development, as well as the therapeutic prospective of modifying NLRP3 inflammasome in the context of anti-cancer therapy. (AU)

Cellular and Molecular Mechanism of Cell Proliferation in Human Gastric Cancer Drug-Resistant Cells After Hyperthermia and Cisplatin: Role of mRNAs and Long-Non-coding RNAs.

BACKGROUND: Since thermo-chemotherapy was suggested as an effective treatment for gastric cancer, we aimed to evaluate the effects of hyperthermia combined with cisplatin (DDP) on the inhibition of human gastric cancer drug-resistant cells in vitro and explore its possible mechanisms. METHODS: SGC-7901/DDP cells were cultured and divided into control, cisplatin, hyperthermia, and hyperthermia combined with cispla- tin groups. Hyperthermia was done at 42°C, 44°C, 46°C, 48°C, and 50°C for 12 h, 24 h, 36 h; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl- 2H-tetrazolium bromide (MTT) assay detected the proliferation of SGC-7901/DDP at different time and temperature, and the apoptotic rate of SGC-7901/DDP cells was evaluated by using Annexin staining assay. High-throughput Chromatin immunoprecipitation (ChIP)- seq was applied to test long non-coding RNA expression in SGC-7901/DDP cells. Then, real-time fluorescence quantitative polymerase chain reaction was used to verify the expression of long non-coding RNA in all groups. RESULTS: Double staining showed that hyperthermia combined with cisplatin increased the rate of early apoptosis of SGC-7901/DDP cells. Long non-coding RNA high-throughput ChIP-seq showed a significantly larger amount of long non-coding RNAs and mRNAs in the cells treated with hyperthermia combined cisplatin group in comparison with the control group. We observed that the upregulated mRNAs and long non-coding RNAs were highly related to immune system response and CD95 signaling pathway in nucleus, and down- regulated mRNAs and long non-coding RNA were highly related to Mammalian target of rapamycin (mTOR) and Tumor necrosis factor (TNF) receptor signaling pathway in cytoplasm. CONCLUSION: Hyperthermia combined with cisplatin reversed the expression of a large number of mRNAs and long non-coding RNAs in human gastric cancer drug-resistant cells. The molecular mechanism of inhibiting the proliferation of human gastric cancer drug- resistant cells may be related to the upregulation of long non-coding RNAs and mRNAs contributed in CD95, mTOR, and TNF receptor signaling pathway.

The role of NLRP3 inflammasome in colorectal cancer: potential therapeutic target.

All phases of carcinogenesis are affected by inflammation. Activation of the inflammasome is a crucial signaling mechanism that leads to acute and chronic inflammation. When specific nucleotide-binding domains, leucine-rich repeat-containing proteins (NLRs) are activated, inflammasomes are formed. The NLRP3 is one of the NLR family members with the most functional characterization. NLRP3 can modulate the immune systems, apoptosis, growth, and/or the gut microbiome to impact cancer development. Colorectal cancer (CRC) is one of the most common cancers, and it begins as a tissue overgrowth on the internal part of the rectum or colon. In vivo and in vitro studies showed that the NLRP3 inflammasome has a role in CRC development due to its broad activity in shaping immune responses. Here, onwards, we focus on the NLRP3 inflammasome role in CRC development, as well as the therapeutic prospective of modifying NLRP3 inflammasome in the context of anti-cancer therapy.

Drug delivery and anticancer activity of biosynthesised mesoporous Fe2 O3 nanoparticles.

Mesoporous magnetic nanoparticles of haematite were synthesised using plant extracts according to bioethics principles. The structural, physical and chemical properties of mesoporous Fe2 O3 nanoparticles synthesised with the green chemistry approach were evaluated by XRD, SEM, EDAX, BET, VSM and HRTEM analysis. Then, their toxicity against normal HUVECs and MCF7 cancer cells was evaluated by MTT assay for 48 h. These biogenic mesoporous magnetic nanoparticles have over 71% of doxorubicin loading efficiency, resulting in a 50% reduction of cancer cells at a 0.5 µg.ml-1 concentration. Therefore, it is suggested that mesoporous magnetic nanoparticles be used as a multifunctional agent in medicine (therapeutic-diagnostic). The produced mesoporous magnetic nanoparticles with its inherent structural properties such as polygonal structure (increasing surface area to particle volume) and porosity with large pore volume became a suitable substrate for loading the anti-cancer drug doxorubicin.

The Therapeutic Potential of Common Herbal and Nano-Based Herbal Formulations against Ovarian Cancer: New Insight into the Current Evidence.

Ovarian cancer (OCa) is characterized as one of the common reasons for cancer-associated death in women globally. This gynecological disorder is chiefly named the "silent killer" due to lacking an association between disease manifestations in the early stages and OCa. Because of the disease recurrence and resistance to common therapies, discovering an effective therapeutic way against the disease is a challenge. According to documents, some popular herbal formulations, such as curcumin, quercetin, and resveratrol, can serve as an anti-cancer agent through different mechanisms. However, these herbal products may be accompanied by some pharmacological limitations, such as poor bioavailability, instability, and weak water solubility. On the contrary, using nano-based material, e.g., nanoparticles (NPs), micelles, liposomes, can significantly solve these limitations. Therefore, in the present study, we will summarize the anti-cancer aspects of these herbal and-nano-based herbal formulations with a focus on their mechanisms against OCa.