IntroductionCisplatin, a chemotherapeutic drug, is widely used for the treatment of various malignant tumors with good effects. However, cisplatin-induced nephrotoxicity is a major dose-limiting factor and a significant adverse event. Mannitol is used to reduce cisplatin-induced nephrotoxicity, which is controversial. This study aimed to evaluate the efficacy and safety of a hydration regimen containing mannitol against cisplatin-induced nephrotoxicity through a meta-analysis.MethodsPotential records from PubMed, EMBASE, Cochrane Library, and ClinicalTrials that met the inclusion criteria were included from inception to May 2021. Cochrane Collaboration tools were used to assess the risk of bias in the included studies. Jadad’s and NOS scores were applied to assess the quality of randomized controlled trials (RCTs) and case-control studies. A random-effects model or fixed-effects model was used depending on the heterogeneity. Subgroup analyses were performed to evaluate the potential study characteristics. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated.ResultsFour RCTs and seven case-control studies involving 4168 patients were included. Pooled results showed that mannitol use could reduce the incidence of cisplatin-induced nephrotoxicity (OR = 0.66, 95% CI [0.45–0.97], p = 0.03), especially reducing grade 3 nephrotoxicity events according to CTCAE 4.0 (OR = 0.37,95% CI [0.16–0.84]). Moreover, mannitol use was not significantly associated with creatinine clearance, serum creatine, and electrolyte disturbance (p > 0.05). Gastrointestinal cancer (OR = 0.36, 95% CI [0.15–0.83], p = 0.02) and urinary tract cancer (OR = 0.32,95% CI [0.14–0.73], p = 0.007) may be more sensitive to mannitol, although the test for overall effect was significantly different (OR = 0.66, 95% CI [0.49–0.89], p = 0.007). For patients with diabetes and hypertension, mannitol may worsen renal function (OR = 1.80, 95% CI [1.18–2.72], p = 0.006; OR = 2.19, 95% CI [1.50, 3.19], p < 0.0001, respectively). Mannitol may have a better protective effect when doses of mannitol were ≥ 25 g (OR = 0.58, 95% CI [0.39–0.88], p = 0.01) and doses of cisplatin < 75 mg/m2 (OR = 0.59, 95% CI [0.36–0.94], p = 0.03). It revealed that mannitol use was likely to cause nausea or vomiting (OR = 1.86, 95% CI [1.20–2.89], p = 0.006).ConclusionCurrent evidence revealed that mannitol was an effective and safe drug to reduce cisplatin-induced nephrotoxicity events, especially Grade 3 events. However, it may cause more nausea/vomiting events and deteriorate renal function in patients with diabetes or hypertension. We also found that mannitol had the best effect when mannitol was ≥ 25 g in total or cisplatin was < 75 mg/m2. Meanwhile, mannitol may have a better effect on gastrointestinal and urinary tract cancers.Systematic Review Registrationcrd. york. ac. uk/PROSPERO, CRD 42021253990

Non-small cell lung cancer is a common respiratory tumor. The mortality rate of lung cancer patients has continued to rise in recent years. Several studies revealed that the expression of melanoma antigen 6 (MAGE-A6) promoted the development of multiple types of cancer. In addition, the suppression of AMPK pathway could restrict the radiosensitization of prostate cancer cells. Inhibition of MAGE-A6 activated the AMPK pathway in colorectal cancer cells. However, whether the MAGE-A6 could regulate the radiosensitivity of non-small cell lung cancer cells by regulating of the AMPK pathway is unclear. In this study, we established the MAGE-A6 knockdown in A549 and H1299 cells. Next, the apoptosis and proliferation of these cells were detected by the flow cytometry analysis and colony formation assay after the irradiation, respectively. Then, the expression of p-AMPKα1 and p-S6K1 in these cells was explored by the western blotting. After that, we inhibited the expression of AMPKα1 in MAGE-A6 knockdown cells. The proliferation and apoptosis of these cells were detected with colony formation assay and flow cytometry analysis. Finally, the tumor formation of these cells was detected in nude mice. Our results showed that inhibition of MAGE-A6 suppressed the proliferation and aggravated the apoptosis of A549 and H1299 cells after the irradiation. Knockdown of MAGE-A6 activated the expression of p-AMPKα1 and repressed the expression of p-S6K1 in these cells. Suppression of AMPKα1 in MAGE-A6 knockdown cells abolished these effects. Knockdown of MAGE-A6 also enhanced the radiosensitivity of these cells in vivo. These results suggested that inhibition of MAGE-A6 promoted the radiosensitivity of non-small cell lung cancer cells by activating AMPK pathway. Therefore, MAGE-6 has the potential to be explored as the therapeutic target for the treatment of non-small cell lung cancer in clinical.

PurposeHepatocellular carcinoma is one of the most predominant malignancies with high fatality rate and its incidence is rising at an alarming rate because of its resistance to radio- and chemotherapy. Indirubin is the major active anti-tumor ingredient of a traditional Chinese herbal medicine. The present study aimed to analyze the effects of indirubin on cell proliferation, migration, invasion, and angiogenesis of tumor-derived endothelial cells (Td-EC).MethodsTd-EC were derived from human umbilical vein endothelial cells (HUVEC) by treating HUVEC with the conditioned medium of human liver cancer cell line HepG2. Cell proliferation, migration, invasion, and angiogenesis were assessed by MTT, wound healing, in vitro cell invasion, and in vitro tube formation assay.ResultsTd-EC were successfully obtained from HUVEC cultured with 50% culture supernatant from serum-starved HepG2 cells. Indirubin significantly inhibited Td-EC proliferation in a dose- and time-dependent manner. Indirubin also inhibited Td-EC migration, invasion, and angiogenesis. However, indirubin’s effects were weaker on HUVEC than Td-EC.ConclusionIndirubin significantly inhibited Td-EC proliferation, migration, invasion, and angiogenesis.

Aiming at the problem encountered in the previous research: during the electrical activity of cardiomyocytes, the influent ions do not seem to be directly derived from the extracellular fluid. We chose to cut in from the colloidal properties of the cells, follow the basic principles of physical chemistry, and establish hypotheses along the derivation of the structural characteristics of cardiomyocytes. Through the surface ion adsorption experiment and patch clamp experiment of living cells, under the condition of sequentially reducing the concentration of Na+ in the extracellular fluid, we observed the exchange and diffusion of adsorbed ions on the cell surface; the changes of inflow INa, ICa-L and action potential; and correlation between results. The results showed that the hypothesis is true. The observed parameter changes were consistent with the fact that during depolarization of cardiomyocytes, the ions of influx were derived from the inference of adsorbed ions on the cell surface; at the same time, it also provided an objective and realistic explanation for the generation of electrocardiogram.

This article explores the effects and mechanisms of magnolol on the proliferation of gastric cancer cells as well as the apoptosis. First, 0 (control group), 20, 40, and 80 /x mol/L magnolol were observed on SGC-7901 cells for 24, 48, and 72 h. We use MTT method to measure the cell viability, and apoptosis and cells were detected by flow cytometry. Cell proliferation inhibition rate, apoptosis and cell cycle experiments showed that P-value < 0.05 means the difference is statistically significant. And the results which compare the control group, the 20, 40, and 80 /x mol/L show that honokiol had lower cell viability (P < 0.01), increased apoptotic rate (P < 0.01), and cell cycle stay in the G1 phase (P < 0.01), so we found that honokiol may suppress the proliferation of SGC-7901 cells and stimulate apoptosis by regulating cyclin and apoptosis-related proteins. With the development of nanomaterials synthesis technology and application in biomedicine, gold magnetic composite nanomaterials have unique properties, so they have been widely concerned in many applications. We combine gold and magnetic nanomaterials through other nanostructures to achieve the integration of diagnosis and treatment of tumors. We have synthesized two kinds of gold magnetic nanocomposites, GNR-PPy-FA nanocomposites. With the role of chemotherapy and heat and light therapy, GNR-PPy-FA nanocomposites have high light-to-heat conversion efficiency. Cell experiments verify the effect of chemotherapy and photothermal treatment of composite nanomaterials. After incubation with gold magnetic composite nanomaterials, the cell survival rate of tumor cells decreased to about 15%. In addition, both types of gold magnetic nanocomposites have the ability to dually target cancer cells, and the modification of folic acid and cancer cell membranes makes the material more biocompatible.