Mechanisms of cancer cell death induction by triptolide: A comprehensive overview.

The need for naturally occurring constituents is driven by the rise in the cancer prevalence and the unpleasant side effects associated with chemotherapeutics. Triptolide, the primary active component of "Tripterygium Wilfordii", has exploited for biological mechanisms and therapeutic potential against various tumors. Based on the recent pre-clinical investigations, triptolide is linked to the induction of death of cancerous cells by triggering cellular apoptosis via inhibiting heat shock protein expression (HSP70), and cyclin dependent kinase (CDKs) by up regulating expression of P21. MKP1, histone methyl transferases and RNA polymerases have all recently identified as potential targets of triptolide in cells. Autophagy, AKT signaling pathway and various pathways involving targeted proteins such as A-disintegrin & metalloprotease-10 (ADAM10), Polycystin-2 (PC-2), dCTP pyro-phosphatase 1 (DCTP1), peroxiredoxin-I (Prx-I), TAK1 binding protein (TAB1), kinase subunit (DNA-PKcs) and the xeroderma-pigmentosum B (XPB or ERCC3) have been exploited. Besides that, triptolide is responsible for enhancing the effectiveness of various chemotherapeutics. In addition, several triptolide moieties, including minnelide and LLDT8, have progressed in investigations on humans for the treatment of cancer. Targeted strategies, such as triptolide conjugation with ligands or triptolide loaded nano-carriers, are efficient techniques to confront toxicities associated with triptolide. We expect and anticipate that advances in near future, regarding combination therapies of triptolide, might be beneficial against cancerous cells.

Therapeutic, diagnostic and prognostic values of TRIM proteins in prostate cancer.

Prostate cancer is the second most prevalent cancer in men worldwide. The TRIM (tripartite motif) family of proteins is involved in the regulation of various cellular processes, including antiviral immunity, apoptosis, and cancer progression. In recent years, several TRIM proteins have been found to play important roles in prostate cancer initiation and progression. TRIM proteins have indicated oncogenic activity in prostate cancer by enhancing androgen or estrogen receptor signaling and promoting cancer cell growth. Inhibition of TRIM proteins has been raised as a potential therapeutic strategy for the treatment of prostate cancer. Overall, these studies suggest that TRIM family proteins exert tumor-promoting effects in prostate cancer, and targeting these proteins can provide a promising therapeutic strategy for prostate cancer treatment. On the other hand, some TRIM proteins can be differentially expressed in prostate cancer cells compared to normal cells, thus providing novel diagnostic/prognostic biomarkers for prostate cancer.

Value of genomics- and radiomics-based machine learning models in the identification of breast cancer molecular subtypes: a systematic review and meta-analysis.

Background: In the era of precision therapy, early classification of breast cancer (BRCA) molecular subtypes has clinical significance for disease management and prognosis. We explored the accuracy of machine learning (ML) models for early classification of BRCA molecular subtypes through a systematic review of the literature currently available. Methods: We retrieved relevant studies published in PubMed, EMBASE, Cochrane, and Web of Science until 15 April 2022. A prediction model risk of bias assessment tool (PROBAST) was applied for the assessment of risk of bias of a genomics-based ML model, and the Radiomics Quality Score (RQS) was simultaneously used to evaluate the quality of this radiomics-based ML model. A random effects model was adopted to analyze the predictive accuracy of genomics-based ML and radiomics-based ML for Luminal A, Luminal B, Basal-like or triple-negative breast cancer (TNBC), and human epidermal growth factor receptor 2 (HER2). The PROSPERO of our study was prospectively registered (CRD42022333611). Results: Of the 38 studies were selected for analysis, 14 ML models were based on gene-transcriptomic, with only 4 external validations; and 43 ML models were based on radiomics, with only 14 external validations. Meta-analysis results showed that c-statistic values of the ML based on radiomics for the identification of BRCA molecular subtypes Luminal A, Luminal B, Basal-like or TNBC, and HER2 were 0.76 [95% confidence interval (CI): 0.60-0.96], 0.78 (95% CI: 0.69-0.87), 0.89 (95% CI: 0.83-0.91), and 0.83 (95% CI: 0.81-0.86), respectively. The c-statistic values of ML based on the gene-transcriptomic analysis cohort for the identification of the previously described BRCA molecular subtypes were 0.96 (95% CI: 0.93-0.99), 0.96 (95% CI: 0.93-0.99), 0.98 (95% CI: 0.95-1.00), and 0.97 (95% CI: 0.96-0.98) respectively. Additionally, the sensitivity of the ML model based on radiomics for each molecular subtype ranged from 0.79 to 0.85, while the sensitivity of the ML model based on gene-transcriptomic was between 0.92 and 0.99. Conclusions: Both radiomics and gene transcriptomics produced ideal effects on BRCA molecular subtype prediction. Compared with radiomics, gene transcriptomics yielded better prediction results, but radiomics was simpler and more convenient from a clinical point of view.

Application of tumor-targeting peptide-decorated polypeptide nanoparticles with doxorubicin to treat osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumor in childhood and adolescence. Currently, surgery combined with chemotherapy is the main treatment for osteosarcoma. However, the long-term survival of patients with metastatic osteosarcoma is unsatisfactory. Therefore, new treatment methods to improve the prognosis of patients with osteosarcoma are required. The present study aimed to develop nanocarriers with both tumor targeting and reduction responsiveness abilities, and to improve the therapeutic effect and reduce toxicity by loading traditional small molecule antitumor drugs. The tumor targeting peptide-decorated, doxorubicin (DOX)-loaded mPEG-P(Phe-co-Cys) nanoparticles were developed successfully through the ring-opening polymerization of amino acids. The peptide VATANST (STP) can specifically bind with vimentin, which is highly expressed on the osteosarcoma cell surface, resulting in tumor targeting effects. The nanoparticle is core-shell structured to protect the loaded DOX during blood flow. The disulfide bonds within the nanoparticles are sensitive to the osteosarcoma microenvironment, which has high glutathione (GSH) levels. Under the enhanced permeability and retention and active tumor targeting effects, the STP-decorated DOX-loaded nanoparticles accumulated in tumor tissues. High GSH levels can rupture disulfide bonds, resulting in the controlled release of DOX, which will cause necrosis of tumor cells. The characteristics of the synthesized nanoparticles, DOX release profiles in vitro and in vivo, cytotoxicity analysis, animal study, and safety evaluation were performed. The nanoparticles could increase the tumor inhibition efficiency against osteosarcoma and reduce the side effects of DOX to major organs. The STP-decorated mPEG-P(Phe-co-Cys) nanoparticles might be a suitable drug delivery system for DOX to treat osteosarcoma.

Anticancer Properties of Different Solvent Extracts of Cucumis melo L. Seeds and Whole Fruit and Their Metabolite Profiling Using HPLC and GC-MS.

Honeydew melon (Cucumis melo L.) is an oval-shaped delicious fruit of one cultivar group of the muskmelon with immense nutritional importance and is extensively consumed by many tropical countries. The effect of various organic solvents on the recovery of phytochemicals from honeydew melon plant fruits and seeds was assessed. Further, High-Performance Liquid Chromatography (HPLC) was used to examine and assess the contents of phenolic acid (gallic acid) and flavonoid (rutin) compounds. The use of gas chromatography-mass spectrometry (GC-MS) analysis explained the presence of volatile phytocompounds in the extracts. The use of organic solvents had a substantial impact on the total dry weight and extract yield. In general, the solvent-extracted constituents remained in the order of methanol>chloroform>distilled water for both honeydew melon seeds and whole fruit. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) was used to assess the cytotoxicity effect against PC3, HCT116, HeLa, and Jurkat cell lines. The chloroform extract exhibited a good cytotoxic activity against all cell lines as compared to other solvent extracts. HPLC analysis revealed the occurrence of gallic acid content of 0.102 ± 0.23 mg/10 mg of dry whole fruit extract, while 10 mg of dry seed extract contained only 0.022 ± 0.12 mg of gallic acid content. Likewise, rutin content was observed to be 0.224 ± 0.31 mg and 0.1916 ± 0.82 mg/10 mg of dry whole fruit and seed extract, respectively. Further, GC-MS analysis revealed the presence of a total of 37 compounds in chloroform extract of whole fruit, while only 14 compounds were found in seed extract. Nevertheless, more examinations are needed to identify and characterize other metabolites from honeydew melon and evaluate their pharmacological importance.

Anticancer and Antibacterial Activities of Silver Nanoparticles (AgNPs) Synthesized from Cucumis melo L.

The current investigation reports the structural and biological evaluation of silver nanoparticles (AgNPs) biosynthesized from the pericarp extract of Cucumis melo L. (muskmelon). The AgNPs were characterized by ultraviolet-visible (UV-Vis) spectrophotometry, XRD (X-ray diffraction), SEM (scanning electron microscopy) and EDAX (energy-dispersive X-ray spectroscopy). The XRD analysis showed that biosynthesized AgNPs were having FCC (face centered cubic) crystalline structures. Further, the SEM and EDAX showed spherically shaped AgNPs having an average size of 25 nm. The AgNPs effectively inhibited the growth of Bacillus subtilis and Escherichia coli. Moreover, the cytotoxic assay of AgNPs revealed effective cytotoxicity against different cancer cells, such as HeLa, HCT-116, PC-3 and Jurkat in a dose reliant way. The cell viability was noticed to range from 50% to 60% with IC50 values ranging from 150 µg/mL to 224 µg/mL. The lower cell viability indicates the toxic effects of biosynthesized AgNPs against these malignant cells. Thus, the current study shows that these biosynthesized AgNPs could be utilized in various medical applications in near future.

Potential applications of nanoparticles for tumor microenvironment remodeling to ameliorate cancer immunotherapy.

In recent years, researchers have made significant innovations in the field of tumor immunotherapy based on the knowledge of biology, oncology, and immunology. Tumor immunotherapy involves the use of immune checkpoint inhibitors and CAR (chimeric antigen receptor)-T cell therapy. As compared with conventional chemotherapy, immunotherapy is a potential approach to induce a more powerful immune response against tumor in the patient suffering from the advanced stage malignancy. Regardless of the developments made, a large number of clinical studies have confirmed that a substantial number of cancer patients still demonstrate non-responsiveness to immunotherapy, mainly due to the immunomodulating interactions of tumor cells with the immunosuppressive tumor microenvironment (iTME). It leads to immune tolerance of tumors and influences the efficacy of immunotherapy. This immune failure could be attributed to a complex immunosuppressive network comprising stromal and inflammatory cells, vessel system, ECM (extracellular matrix) and the cytokines released in tumor microenvironment (TME). The antitumor immune activity can be enhanced at different stages of tumor development by selective suppression of inhibitory pathways in the TME. This specific task can be achieved by using nano-sized drug delivery tools which are specific in their action and biocompatible in nature. Several recent studies have described the use of nanoparticles for iTME remodeling through the specific elimination of immunosuppressive cells, obstructing immune checkpoints, promotion of inflammatory cytokines, and amending the regulatory cells of the immune system. The efficacy of current immunotherapy can be improved by nanoparticle-mediated remodeling of iTME.

[Effects of electroacupuncture at "Weizhong" (BL 40) on morphology and expression of CK and IL-17 in rats with bupivacaine-induced multifidus muscle injury].

OBJECTIVE: To observe effects of electroacupuncture (EA) at "Weizhong" (BL 40) on morphology and expression of creatine kinase (CK) and interleukin-17 (IL-17) in rats with bupivacaine-induced multifidus muscle injury. METHODS: A total of 32 male SD rats were randomly divided into a control group, a model group, a Weizhong group and a Shenshu group, 8 rats in each one. The rats in the model group, Weizhong group and Shenshu group were treated with intramuscular injection of 0.5% bupivacaine to establish the model of multifidus muscle injury; the rats in the control group were injected with 0.9% sodium chloride solution. The rats in the Weizhong group and Shenshu group were treated with EA (2 Hz/10 Hz in frequency, 1~2 mA in intensity) at "Weizhong" (BL 40) and "Shenshu" (BL 23), 20 min per treatment. No treatment was given in the control group and model group. After 14-day treatment of EA, the inflammatory cell count, scar tissues area and muscle fiber cross sectional area of multifidus muscle were observed with HE and Masson staining method. The activity of CK and serum content of IL-17 were test with enzyme-linked immunosorbent assay (ELISA) method; the expression of IL-17 in multifidus muscle was measured with immunohistochcmical method. RESULTS: After intervention, the inflammatory cell count and scar tissues area in the model group, Weizhong group and Shenshu group were higher than those in the control group (all P<0.01), but the muscle fiber cross sectional area was significantly reduced (all P<0.01); the inflammatory cell count and scar tissues area in the Weizhong group and Shenshu group were lower than those in the model group (all P<0.01), and the muscle fiber cross sectional area was significantly increased (P<0.01, P<0.05). After intervention, the expression of IL-17 in multifidus muscle, serum content of IL-7 and activity of CK in the model group, Weizhong group and Shenshu group were higher than those in the control group (all P<0.01); the expression of IL-17 in multifidus muscle, serum content of IL-7 and activity of CK in the Weizhong group and Shenshu group were lower than those in the model group (P<0.01, P<0.05); compared with the Shenshu group, the down-regulation of IL-17 was more obvisous in the Weizhong group (P<0.01). CONCLUSION: EA at "Weizhong" (BL 40) can down-regulate the overexpression of serum CK and IL-17, alleviate inflammation reaction and improve the repair of multifidus muscle.