Mechanisms of action of the BCL-2 inhibitor venetoclax in multiple myeloma: a literature review.

Abnormal cellular apoptosis plays a pivotal role in the pathogenesis of Multiple Myeloma (MM). Over the years, BCL-2, a crucial anti-apoptotic protein, has garnered significant attention in MM therapeutic research. Venetoclax (VTC), a small-molecule targeted agent, effectively inhibits BCL-2, promoting the programmed death of cancerous cells. While VTC has been employed to treat various hematological malignancies, its particular efficacy in MM has showcased its potential for broader clinical applications. In this review, we delve into the intricacies of how VTC modulates apoptosis in MM cells by targeting BCL-2 and the overarching influence of the BCL-2 protein family in MM apoptosis regulation. Our findings highlight the nuanced interplay between VTC, BCL-2, and MM, offering insights that may pave the way for optimizing therapeutic strategies. Through this comprehensive analysis, we aim to lay a solid groundwork for future explorations into VTC's clinical applications and the profound effects of BCL-2 on cellular apoptosis.

A literature review: mechanisms of antitumor pharmacological action of leonurine alkaloid.

Leonurine refers to the desiccated aerial portion of a plant in the Labiatae family. The primary bioactive constituent of Leonurine is an alkaloid, Leonurine alkaloid (Leo), renowned for its substantial therapeutic efficacy in the treatment of gynecological disorders, in addition to its broad-spectrum antineoplastic capabilities. Over recent years, the pharmacodynamic mechanisms of Leo have garnered escalating scholarly interest. Leo exhibits its anticancer potential by means of an array of mechanisms, encompassing the inhibition of neoplastic cell proliferation, induction of both apoptosis and autophagy, and the containment of oncogenic cell invasion and migration. The key signal transduction pathways implicated in these processes include the Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL), the Phosphoinositide3-Kinase/Serine/Threonine Protein Kinase (PI3K/AKT), the Signal Transducer and Activator of Transcription 3 (STAT3), and the Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase (MAP/ERK). This paper commences with an exploration of the principal oncogenic cellular behaviors influenced by Leo and the associated signal transduction pathways, thereby scrutinizing the mechanisms of Leo in the antineoplastic sequence of events. The intention is to offer theoretical reinforcement for the elucidation of more profound mechanisms underpinning Leo's anticancer potential and correlating pharmaceutical development.

The impact of concurrent bacterial lung infection on immunotherapy in patients with non-small cell lung cancer: a retrospective cohort study.

Objective: To find out how bacterial lung infections (BLI) affect the effectiveness of therapy and the rate of pneumonia caused by pneumonia related to checkpoint inhibitors (CIP) in patients with non-small cell lung cancer (NSCLC) who are getting immunotherapy with checkpoint inhibitors (ICIs). Patients and methods: 507 NSCLC patients who received at least two ICI treatments between June 2020 and December 2022 at the Affiliated Hospital of Kunming University of Science and Technology(AHKUST) were included in a retrospective cohort study. Based on whether there was a concurrent BLI diagnosis from high-resolution CT scans of the chest, the patients were divided into two groups: 238 in the NSCLC with BLI group (NSCLC-BLI group), and 269 in the NSCLC alone group. The collected therapeutic outcome measures included the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the incidence rate of CIP. We analyzed the effect of BLI on the therapeutic efficacy of ICI treatment and the incidence rate of CIP in NSCLC patients.Inclusion criteria based on NSCLC patients staged I to IV according to the 8th edition of the International Association for Lung Cancer Research (IASLC). Results: The NSCLC-BLI group showed superior ORR to the NSCLC group when treated with ICIs. Multifactorial logistic regression and Cox analyses, adjusted for confounders, identified BLI as an independent positive prognostic factor for ORR (HR=0.482, 95%CI: 0.391-0.550; P<0.001) and PFS (HR=0.619; 95%CI: 0.551-0.771; P<0.001). No correlation between BLI and OS was found. Out of 26 cases of CIP, 12 were in the NSCLC-BLI group and 14 in the NSCLC group, with no significant difference in incidence (P=0.145). Conclusion: NSCLC patients with BLI receiving ICI treatment show superior ORR and PFS compared to NSCLC alone without an increased CIP risk, positioning BLI as a predictive factor for improved outcomes in NSCLC patients receiving ICIs. However, the study has limitations including its retrospective nature and lacking data on BLI bacteria types and levels, which could influence therapy outcomes.

Reprogramming of Treg cells in the inflammatory microenvironment during immunotherapy: a literature review.

Regulatory T cells (Treg), as members of CD4+ T cells, have garnered extensive attention in the research of tumor progression. Treg cells have the function of inhibiting the immune effector cells, preventing tissue damage, and suppressing inflammation. Under the stimulation of the tumor inflammatory microenvironment (IM), the reprogramming of Treg cells enhances their suppression of immune responses, ultimately promoting tumor immune escape or tumor progression. Reducing the number of Treg cells in the IM or lowering the activity of Treg cells while preventing their reprogramming, can help promote the body's anti-tumor immune responses. This review introduces a reprogramming mechanism of Treg cells in the IM; and discusses the regulation of Treg cells on tumor progression. The control of Treg cells and the response to Treg inflammatory reprogramming in tumor immunotherapy are analyzed and countermeasures are proposed. This work will provide a foundation for downregulating the immunosuppressive role of Treg in the inflammatory environment in future tumor immunotherapy.

Therapeutic efficacy of rare earth carbonate with chemoradiotherapy in late-stage non-small cell lung cancer: a cohort prospective study.

Objective: To compare the therapeutic effects and adverse reactions of sterilizing rare earth carbonate combined with concurrent chemoradiotherapy and simple concurrent chemoradiotherapy in the treatment of late-stage non-small cell lung cancer (NSCLC), and to analyze the reasons for the differences. Method: A total of 817 patients with pathologically diagnosed late-stage NSCLC from June 1, 2021 to December 30, 2022, in the affiliated hospital of Kunming University of Science and Technology, were selected. They were randomly divided into a control group of 394 people and an experimental group of 423 people. The control group was given concurrent chemoradiotherapy (cisplatin + etoposide), while the experimental group simultaneously took a low dose of sterilized rare earth carbonate (0.05mg/Kg). The χ² test and Fisher's test were used to compare the clinical pathological features, objective response rate (ORR), ECOG score, and adverse reactions of the two groups of patients, while survival analysis was used to compare the progression-free survival (PFS) of the two groups. Cox regression analysis was used to test factors related to prognosis. Results: The differences in clinical pathological features between the two groups of patients were not statistically significant, with all P>0.05. The ORR of the control group was 45.18% (178/394), and the experimental group was 89.83% (380/423), with a statistically significant difference (P=0.001). After treatment, the ECOG score of the experimental group was lower than that of the control group, P<0.001. The adverse reaction grading of patients in both groups was below level 3 after treatment, and no treatment-related fatalities occurred. The risk of pulmonary infection and bone marrow suppression in the experimental group was lower than that in the control group. Conclusion: In late-stage NSCLC patients, compared with simple concurrent chemoradiotherapy, the combination of concurrent chemoradiotherapy and sterilizing rare earth carbonate can significantly improve the short-term therapeutic effect and prognosis of patients, with good safety.

Comparative performance of green rusts generated in Fe0-electrocoagulation for Cd2+ removal from high salinity wastewater: Mechanisms and optimization.

The treatment of wastewater containing high concentration of inorganic salts has always been one of the focuses of environmental researchers. In this work, the effect of Cl- and SO42- on the removal of Cd2+ from wastewater using Fe0-electrocoagulation (Fe0-EC) were investigated by evaluating the transformation of Fe mineral. The experimental results indicated that the removal of Cd2+ from wastewater was depended on the property of Fe minerals. The generation of sulfate green rust (GRSO4) produced in the presence of SO42- showed stronger adsorption than the chloride green rust (GRCl) for Cd2+, and GRSO4 was obtained even in the mixture Cl- and SO42- solutions, because Fe(II)-Fe(III) GRs (layered double hydroxides, LDHs) showed stronger affinity for divalent SO42- than monovalent Cl-. High concentration of inorganic anions in wastewater resulted in the negative charged Fe flocs. High concentration of Cl- promoted the oxidation of Fe(II) to Fe(III) by chlorine-containing oxidants, and increased the proportion of Fe(III)/Fe(II) in Fe flocs, secondary Fe mineral magnetite (Fe3O4) was formed because of the increase of pH. Therefore, the presence of GRSO4 intermediate increased the Cd2+ removal by adsorption (coagulation and coprecipitation), and then the generated GRSO4 were gradually transformed into lepidocrocite (γ-FeOOH) by oxygen from air. Finally, the parameter optimization were conducted by adjusting the ratio of Cl- and SO42- (RC:S), current density (j), initial pH (pHi), initial Cd2+ concentration (C0), and temperature (T0). The removal efficiency of Cd2+ reached 99.5% after 10 min Fe0-EC under the optimal parameters: RC:S = 25:50 mmoL/mmol, j = 6 mA/cm2, pHi = 7-9, and T0 = 40 °C.

Adsorption performance and mechanisms of Pb(II), Cd(II), and Mn(II) removal by a ß-cyclodextrin derivative.

In this study, the novel adsorbent PVA-TA-ßCD was synthesized via thermal cross-linking between polyvinyl alcohol and ß-cyclodextrin. The characterization methods SEM-EDS, FTIR, and XPS were adopted to characterize the adsorbent. The effect of pH, contact time, initial concentrations, and temperature during the adsorption of Pb(II), Cd(II), and Mn(II) onto the PVA-TA-ßCD was also investigated. In a single-component system, the data fitted well to pseudo-second-order, and film diffusion and intra-particle diffusion both played important roles in the adsorption process. As for isotherm study, it showed a heterogeneous adsorption capacity of 199.11, 116.52, and 90.28 mg g-1 for the Pb(II), Cd(II), and Mn(II), respectively. Competition between the ions existed in a multi-component system; however, owing to the stronger affinity of the PVA-TA-ßCD for Pb(II) relative to Cd(II) and Mn(II), the Pb(II) adsorption onto the PVA-TA-ßCD was less affected by the addition of the other metals, which could be effectively explained by the hard and soft acid and base theory (HSAB). Furthermore, PVA-TA-ßCD showed good reusability throughout regeneration experiments.

Optimization and assessment of Fe-electrocoagulation for the removal of potentially toxic metals from real smelting wastewater.

This study evaluates the performance of a continuous electrocoagulation system (batch recirculation mode) on the simultaneous removal of Zn2+, Cd2+, and Mn2+ from real smelting wastewater by using Fe-Fe electrodes. Several parameters are evaluated to determine the optimal operating conditions. These conditions include the type of power supply (p), current density (j), aeration intensity (v), flow rate (u), and anions (SO42- and SO32-). At current density = 10-20 mA/cm2, the DC power supply performs better than the APC power supply in treating wastewater. Current density positively affects the removal of heavy metals by increasing the production of Fe hydroxides. However, a lower aeration intensity of 0.5-1 L/min and a flow rate of 1 L/min are considerable because of flotation and turbulence, respectively. Moreover, adding SO42- and SO32- contributes to the precipitation of metal hydroxides. Lastly, the optimal parameters for the DC power supply used to treat smelting wastewater are as follows: pHi, 6.9; current density, 15 mA/cm2; aeration intensity, 0.5 L/min; flow rate, 1 L/min; SO42-, 25 mmol/L; and time, 120 min. The highest removal efficiency for each of Zn2+, Cd2+, and Mn2+ reached 99.93%, 97.15%, and 85.46%, with electrical energy consumption = 14.76 kWh/m3 (42 kWh/kg), electrode consumption = 2.09 kg/m3 (5.88 kg/kg), and operational cost = 2.2 US$/m3 (6.21 US$/kg), respectively.

Simultaneous removal of cadmium, zinc and manganese using electrocoagulation: Influence of operating parameters and electrolyte nature.

In the present study, the influence of operating parameters and electrolyte nature on the simultaneous removal of toxic metals (cadmium, zinc and manganese) from synthetic smelting wastewater by batch electrocoagulation was investigated. This wastewater contained high concentrations of anion-cation electrolytes. Results indicated that the efficiency of heavy metals removal can be enhanced by increasing the solution pH and current density. The Fe-Fe electrode combination is more effective than the other combinations (Al-Al, Al-Fe and Fe-Al). The interaction of heavy metal ions showed that the increase of initial Zn2+ concentration adversely affects on Cd2+ removal. In addition, the single chloride system exhibits the optimum removal efficiency on Mn2+. Single sulfate and binary anion systems exert a more positive effect on Cd2+ and Zn2+ removal because of the stronger charge neutralization and destabilization of iron hydroxide flocs. Increases of Ca2+ and Mg2+ ions exert a significant negative effect on metal removal. However, the addition of a small amount of sodium chloride into a high sulfate and hardness solution can accelerate the removal of heavy metals. Finally, the sludge samples generated from electrocoagulation were characterized by XRD and SEM-EDS analyses.