Effects of Rifampicin Plus Levofloxacin or Isoniazid on Immune Function of Patients with Pulmonary Tuberculosis.

Context: Due to the different effects of various drugs and the lack of authoritative and unified guidelines in clinical practice, the choice of therapeutic drugs for pulmonary tuberculosis (TB) remains controversial. Rifampicin, levofloxacin, and isoniazid are all anti-TB drugs. However, no comparative studies of the treatment effects of rifampicin + levofloxacin and rifampicin + isoniazid have occurred. Objective: The study intended to analyze the therapeutic effects of rifampicin + levofloxacin compared to rifampicin + isoniazid in the treatment of pulmonary TB to provide a clinical reference, which could provide new references for future clinical treatment of the disease. Design: The research team conducted a prospective controlled study. Setting: The study took place at Zibo Zhoucun District People's Hospital in Zibo, China. Participants: Participants were 100 patients with pulmonary TB admitted to the hospital between March 2021 and December 2022. Interventions: The research team assigned participants to one of two groups: (1) the intervention group, with 56 participants who received rifampicin + levofloxacin therapy, and (2) the control group, with 44 participants who received rifampicin + isoniazid. Outcome Measures: The research team measured: (1) clinical efficacy, (2) incidence of adverse reactions, (3) changes in inflammatory factors, (4) changes in immunoglobulins (Igs), and (5) changes in T lymphocyte subsets. Results: The intervention group's total effective rate for treatment was significantly higher than that of the control group (P = .049). However, no significant difference existed between the groups in the incidence of adverse reactions (P > .05). Postintervention, the intervention group's inflammatory factors-IL-6, TNF-α, hs-CRP, and ß-EP-were significantly lower and its immunoglobulins (Igs) G/A/M (IgG/A/M) were significantly higher than those of the control group (P < .05). In addition, the intervention group's T lymphocyte subpopulations of CD3+ and CD4+ and CD4+/CD8+ were significantly higher and CD8+ was significantly lower than those in the control group (P < .05). In other words, the intervention group had a better immune function. Conclusions: Compared with rifampicin + isoniazid, rifampicin + levofloxacin had a better clinical effect in the treatment of pulmonary TB and could effectively regulate patients' immune functions and inhibit inflammatory reactions. The current research team recommends that rifampicin + levofloxacin become the preferred treatment for pulmonary TB in the absence of a drug allergy.

Vitamin C inhibits the growth of colorectal cancer cell HCT116 and reverses the glucose-induced oncogenic effect by downregulating the Warburg effect.

Malnutrition caused by insufficient nutritional supply may significantly hinder the quality of life among cancer patients. Sugar provides energy and nutritional support, but it also promotes cancer growth. Warburg effect is the reprogrammed glucose metabolic mode of cancer cells that meets the intensified ATP demand and biosynthesis. Vitamin C (VC) has anti-tumor effect. However, the relationship between cytotoxicity of VC on cancer cells and Warburg effect remains elusive, the effect of VC on glucose-induced oncogenic effect is also unclear. Based on colorectal cancer cell HCT116, our finding revealed that the discrepant oncogenic effect of different sugar is closely related to the intensification of Warburg effect, with glucose being the potent oncogenic component. Notably, as a potential Warburg effect inhibitor, VC suppressed cancer growth in a concentration-dependent manner and further reversed the glucose-induced oncogenic effect. Furthermore, VC protected tumor-bearing mice from insulin sensitivity impairment and inflammatory imbalance. These findings imply that VC might be a useful adjuvant treatment for cancer patients seeking to optimize nutritional support.

A Platelet Intelligent Vehicle with Navigation for Cancer Photothermal-Chemotherapy.

Controllable and visible delivery of therapeutic agents is critical for tumor precise therapy. Tumor targeting and deep penetration of therapeutic agents are still challenging issues for controllable delivery. Visible drug delivery with imaging navigation can optimize the treatment window for personalized medicine. Herein, a biomimetic platelet intelligent vehicle with navigation (IRDNP-PLT) was developed to achieve controllable and visible delivery with a navigation system, a driving system, and a loading system. The platelets acted as engines and drug repositories to exert the target driving and delivery functions. The fluorescent photothermal agent IR-820 was introduced in the platform to offer an imaging navigation for the intelligent platelet vehicle in addition to photothermal therapy. The nanodrug-loaded platelets enabled efficient drug loading and controlled release of the therapeutic payload by encapsulating photothermal-/pH-sensitive chemotherapeutic nanoparticles (PDA@Dox NPs). In in vivo experiments on 4T1 tumor-bearing mice models, IRDNP-PLT performed well in tumor targeting and showed excellent therapeutic efficacy and tumor recurrence prevention ability. The intelligent platelet vehicle achieved the functions of tumor targeting and deep penetration, fluorescence imaging guidance, photocontrolled drug release, and chemo-photothermal combination therapy, suggesting the advancement for tumor precise delivery and efficient therapy.

Fasting Plasma Glucose and Coronary Heart Disease in a Rural Population of North Henan, China.

Even in individuals without diabetes, the incidence of coronary heart disease (CHD) increases with the rise in fasting plasma glucose (FPG); however, the threshold of FPG for CHD in rural areas of China is unclear. We retrospectively examined 2,987 people. Coronary angiography records were used to determine the presence of CHD as well as its severity. Risk factors for CHD and the relationship between different levels of FPG and CHD were analyzed. After adjusting for age, hypertension, dyslipidemia, smoking, drinking, chronic kidney disease, and previous ischemic stroke, the incidence of CHD in nondiabetic women began to increase when FPG exceeded 5.2 mmol/L (odds ratio (OR) = 1.438, 95% confidence interval (CI) = 1.099-1.880, p=0.008), and the degree of coronary artery lesions also became more severe (OR = 1.406, 95% CI = 1.107-1.788, p=0.005). However, no such correlations were found in nondiabetic men. In conclusion, among the nondiabetic women in rural areas of northern Henan, both the incidence of CHD and the severity of lesions increased when FPG levels were greater than 5.2 mmol/L, while no significant correlation between FPG and CHD was observed in diabetes-free men.

Tumor targeted combination therapy mediated by functional macrophages under fluorescence imaging guidance.

Imaging-guiding and targeted drug delivery to tumors are essential for precision cancer therapy, which is a challenging goal to achieve extraordinary therapeutic efficacy. Functional live cells-based delivery systems are expected to play an important role in imaging-guiding and targeted drug delivery. Herein, we fabricated a delivery system mediated by IR-820 conjugated macrophages for tumor targeted combination therapy under fluorescence imaging guidance. The functional macrophages by nature could cross the barriers and recruit into tumors, and serve as host cells to targeted deliver drugs to tumors. The pH-sensitive doxorubicin nanoparticles were engulfed by the macrophages to enhance the drug loading and decrease the damage on host cells. IR-820 was anchored into macrophages cytoplasm to achieve the dual function of photothermal therapy and fluorescence imaging guidance. With Balb/C mice bearing murine breast tumor (4 T1) as models, the functional macrophages for their innate tumor tropism could targeted transport these therapeutic drugs into tumor site to exert efficient chemo-photothermal combination therapy. Moreover, fluorescence imaging-guided drug delivery was employed as the visible strategy to provide the optimized therapeutic window based on the fluorescence of IR-820. The multi-functional macrophages-mediated delivery system would provide a potential for precise and targeted delivery of combination therapy.

Fluorescence imaging guided CpG nanoparticles-loaded IR820-hydrogel for synergistic photothermal immunotherapy.

As synergistic photothermal immunotherapy has developed as one of the most attractive strategies for cancer therapy, it is crucial to design an effective photothermal immunotherapy system to enhance the synergistic anti-tumor effect and reveal the essential role of each treatment. In this study, we designed CpG self-crosslinked nanoparticles-loaded IR820-conjugated hydrogel with dual self-fluorescence to exert the combined photothermal-immunotherapy. IR820-hydrogel can be effective for hyperthermia to eliminate the primary tumor based on its comprehensive coverage and generated photothermal-induced tumor antigens for assisted immunotherapy. CpG self-crosslinked nanoparticles improved the immune response of adjuvant against melanoma without extra nano-carriers. The synergistic photothermal immunotherapy was achieved by the merging of CpG self-crosslinked nanoparticles and IR820-hydrogel. A possible mechanism of combined antitumor effect was further revealed by analyzing immune cells including CD8 +T cells, DCs, B cells, Treg and MDSC in tumor microenvironment. The specific antitumor immunity was provoked to remove the tumor residues and ultimately the combined treatment mode achieved more effective systemic therapeutic effect than either photothermal therapy or immunotherapy alone. Furthermore, self-fluorescent IR820-hydrogel and CpG nanoparticles exerted the imaging-guided combined photothermal-immunotherapy by the dual fluorescence imaging method without additional fluorescent labeling. This visible combined photothermal-immunotherapy offers a potential for precise cancer treatment.

A dual fluorescent reverse targeting drug delivery system based on curcumin-loaded ovalbumin nanoparticles for allergy treatment.

A reverse targeting drug delivery based on antigen-modified nanoparticles provided an innovative strategy for effectively alleviating or inhibiting immune response. In this study, a dual fluorescent reverse targeting drug delivery system based on curcumin-loaded ovalbumin nanoparticles is developed for allergy treatment. The self-crosslinked ovalbumin nanoparticles achieved the double function of reverse targeting and sustained delivery carriers to maximize the anti-allergy of curcumin. Using a murine model of ovalbumin-induced allergy, this drug delivery system suppressed antigen-specific IgG1 and IgE production, inhibited CD4+ T activity, and decreased the level of ovalbumin-sensitized memory B cells. The curcumin-loaded ovalbumin nanoparticles exert stronger and more effective treatment on the immunomodulatory role. Furthermore, fluorescence imaging in vivo can reveal the precise delivery process for the effective allergy immunotherapy. The dual fluorescent reverse targeting delivery system provided a significant potential for the visible treatment of allergy with the merged functions of targeting, vehicles and fluorescence.

Fabrication of Multifoliate PtRu Bimetallic Nanocomplexes for Computed Tomography Imaging and Enhanced Synergistic Thermoradiotherapy.

To improve the efficiency of cancer therapy, we developed multifoliate PEGylated PtRu bimetallic nanocomplexes (PtRu-PEG BNCs) as multifunctional theranostic nanoagents for computed tomography (CT) imaging and synergistic thermoradiotherapy. The synthesized PtRu-PEG BNCs with uniform size and morphology exhibit excellent stability, notable photothermal effect, and good biocompatibility. As compared with other platinum nanomaterials, the PtRu-PEG BNCs are able to absorb near-infrared laser energy and present excellent photothermal conversion efficiency (44.5%). Multifoliate PtRu-PEG BNCs can be applied to CT imaging and radiotherapy (RT) because of the presence of platinum. Unlike a single therapy method, the integration of photothermal therapy with RT can effectively induce cell apoptosis and generate an obvious synergistic effect. Hence, the as-prepared nanocomplexes can be used as multifunctional theranostic nanoagents.

pH-sensitive charge-conversional and NIR responsive bubble-generating liposomal system for synergetic thermo-chemotherapy.

A charge-conversional and NIR responsive rapid release liposomal system (PSD/DOX/Cypate-BTSL) was developed to enhance therapeutic efficacy of cancer therapy. The cationic liposomes containing Cypate, doxorubicin (DOX) and NH4HCO3 were shielded by pH-sensitive poly(methacryloyl sulfadimethoxine) (PSD) through electrostatic interaction at pH 7.4. At the tumor site (pH 6.5), PSD was deshielded and the liposomes displayed pH-sensitive charge reversal capability. The DOX released from PSD/DOX/Cypate-BTSL with irradiation was markedly higher than the other groups, indicating NIR irradiation and NH4HCO3 had a significant effect on the drug release. After irradiation, the hyperthermia induced by Cypate could produce CO2 bubbles quickly on account of the decomposition of NH4HCO3, achieving the rapid drug release. In 4T1 cells, PSD/DOX/Cypate-BTSL improved cellular uptake and cytotoxicity with irradiation at pH 6.5. In vivo results implied that the liposomes with irradiation could efficiently enhance the tumor accumulation and antitumor efficacy, and reduce systemic side effects of DOX. In conclusion, PSD/DOX/Cypate-BTSL is a promising candidate as a carrier for synergistic effects of PTT and chemotherapy.

A novel lipopolysaccharide-antagonizing aptamer protects mice against endotoxemia.

A growing number of researchers have recognized the importance of using lipopolysaccharide (LPS) as target for the prevention and treatment of sepsis. However, no drugs targeting LPS have been applied clinically. In this study, LPS-inhibiting aptamers were screened by Systematic Evolution of Ligands by Exponential Enrichment (SELEX), and their therapeutic effects for experimental sepsis were observed. After 12 rounds of screening, 46 sequences were obtained. Primary structure analysis indicated that they had identical sequences, partly conserved sequences, or non-conserved sequences. Secondary structure analysis showed these sequences usually contained hairpin or stem-loop structures. Aptamer 19 significantly decreased NF-kappaB activation of monocytes challenged by LPS and reduced the IL-1 and TNF-alpha concentration in the media of LPS-challenged monocytes. Furthermore, aptamer 19 significantly increased the survival rate of mice with endotoxemia. The results suggest that a novel LPS antagonizing aptamer was obtained by SELEX, which successfully treated experimental sepsis.