In Situ Formed Microalgae-Integrated Living Hydrogel for Enhanced Tumor Starvation Therapy and Immunotherapy through Photosynthetic Oxygenation.

The effectiveness of various cancer therapies for solid tumors is substantially limited by the highly hypoxic tumor microenvironment (TME). Here, a microalgae-integrated living hydrogel (ACG gel) is developed to concurrently enhance hypoxia-constrained tumor starvation therapy and immunotherapy. The ACG gel is formed in situ following intratumoral injection of a biohybrid fluid composed of alginate, Chlorella sorokiniana, and glucose oxidase, facilitated by the crossing-linking between divalent ions within tumors and alginate. The microalgae Chlorella sorokiniana embedded in ACG gel generate abundant oxygen through photosynthesis, enhancing glucose oxidase-catalyzed glucose consumption and shifting the TME from immunosuppressive to immunopermissive status, thus reducing the tumor cell energy supply and boosting antitumor immunity. In murine 4T1 tumor models, the ACG gel significantly suppresses tumor growth and effectively prevents postoperative tumor recurrence. This study, leveraging microalgae as natural oxygenerators, provides a versatile and universal strategy for the development of oxygen-dependent tumor therapies.

Nanoparticles Hitchhike on Monocytes for Glioblastoma Treatment after Low-Dose Radiotherapy.

Glioblastomas (GBMs) are aggressive primary brain tumors with fatal outcome. Traditional chemo-radiotherapy has poor therapeutic effect and significant side effects, due to the drug and radiotherapy (RT) resistance, natural blood-brain barrier, and high-dose RT damage. Even more, tumor-associated monocytes (macrophages and microglia, TAMs) constitute up to 30%-50% of the GBM cellular content, and the tumor microenvironment (TME) in GBM is extremely immunosuppressive. Here, we synthesized nanoparticles (D@MLL) that hitchhike on circulating monocytes to target intracranial GBMs with the assistance of low-dose RT. The chemical construction of D@MLL was DOX·HCl loaded MMP-2 peptide-liposome, which could target monocytes by the surface modified lipoteichoic acid. First, low-dose RT at the tumor site increases monocyte chemotaxis and induces M1 type polarization of TAMs. Subsequently, the intravenous injected D@MLL targets circulating monocytes and hitchhikes with them to the central site of the GBM area. DOX·HCl was then released by the MMP-2 response, inducing immunogenic cell death, releasing calreticulin and high-mobility group box 1. This further contributed to TAMs M1-type polarization, dendritic cell maturation, and T cell activation. This study demonstrates the therapeutic advantages of D@MLL delivered by endogenous monocytes to GBM sites after low-dose RT, and it provides a high-precision treatment for GBMs.

A Microbial Community Cultured in Gradient Hydrogel for Investigating Gut Microbiome-Drug Interaction and Guiding Therapeutic Decisions.

Despite the recognition that the gut microbiota acts a clinically significant role in cancer chemotherapy, both mechanistic understanding and translational research are still limited. Maximizing drug efficacy requires an in-depth understanding of how the microbiota contributes to therapeutic responses, while microbiota modulation is hindered by the complexity of the human body. To address this issue, a 3D experimental model named engineered microbiota (EM) is reported for bridging microbiota-drug interaction research and therapeutic decision-making. EM can be manipulated in vitro and faithfully recapitulate the human gut microbiota at the genus/species level while allowing co-culture with cells, organoids, and isolated tissues for testing drug responses. Examination of various clinical and experimental drugs by EM reveales that the gut microbiota affects drug efficacy through three pathways: immunological effects, bioaccumulation, and drug metabolism. Guided by discovered mechanisms, custom-tailored strategies are adopted to maximize the therapeutic efficacy of drugs on orthotopic tumor models with patient-derived gut microbiota. These strategies include immune synergy, nanoparticle encapsulation, and host-guest complex formation, respectively. Given the important role of the gut microbiota in influencing drug efficacy, EM will likely become an indispensable tool to guide drug translation and clinical decision-making.

The retrospective research of enteral nutrition with medium-chain triglyceride and total parenteral nutrition support of postoperative chylothorax in adults.

BACKGROUND: Chylothorax is caused by thoracic lymphatic system injuries that leads to the lymph extravasating into the thoracic cavity. There are few reports comparing the therapeutic effects of enteral nutrition with medium-chain triglyceride and total parenteral nutrition, and the results are inconsistent. Our study aimed to research the optimum nutrition support method for chylothorax. STUDY DESIGN: We retrospectively reviewed 35 chylothorax patients after heart and chest surgery from 2014 to 2018, at West China Hospital of Sichuan University, among them there were 27 post-heart surgery patients. We analyzed the therapeutic effects and costs of enteral nutrition with medium-chain triglyceride (E group) and total parenteral nutrition (T group) for chylothorax. RESULTS: The results were similar in patients with all surgeries and patients with only post heart surgery. The total cost during hospitalization in E group was higher than T group (P < 0.01), whereas the nutrition support cost was lower (P < 0.001). The length of hospital stay was longer in E group than T group (P > 0.05). Time from admission to surgery was shorter and from surgery to chylothorax diagnosis was longer in E group compared with T group. Time to resolution and removal of drainage was shorter in E group than T group but the differences were not significant. CONCLUSION: The therapeutic effects in enteral nutrition with medium-chain triglyceride and total parenteral nutrition had no obvious differences. Moreover, enteral nutrition with medium-chain triglyceride is safer and more economical. Therefore, we suggest that enteral nutrition with medium-chain triglyceride could be the first choice to treat postoperative chylothorax when the gastrointestinal tract function is allowed, and this result could be considered for postoperative chylous ascites.

Incidence and Nutritional Management of Chylothorax after Surgery for Congenital Heart Diseases in Children.

BACKGROUND: Chylothorax is caused by thoracic lymphatic system injury that leads to lymph extravasates in the thoracic cavity. Cardiac surgery was the most common cause. Reports comparing therapeutic effects between enteral nutrition (EN) with medium-chain triglycerides (MCT) and total parenteral nutrition (TPN) are few and inconsistent. Our study aimed to analyze the incidence of chylothorax in children in our hospital and optimum nutritional management modalities. METHODS: We retrospectively reviewed the medical records of children admitted to our hospital with a diagnosis of chylothorax from 2014 to 2018. We analyzed the incidence of chylothorax, therapeutic effectiveness, and cost effectiveness of EN with MCT or TPN. RESULTS: 136 patients with chylothorax after surgery for congenital heart disease (CHD) were identified from 172 patients with chylothorax (79.07%); chylothorax occurred in 5.62% of all 2420 congenital heart disease surgeries that were performed during that period. Tetralogy of Fallot (TOF), ventricular septal defect (VSD), and double-outlet right ventricle (DORV) were the most common primary diagnoses. Fontan surgery, TOF repair, and VSD repair were the most common primary procedures. We enrolled 45 patients with cured chylothorax. Nutrition support costs in the EN with MCT group (n = 28) were significantly lower than in the TPN group (n = 17) (P = .000). Time to resolution and time to removal of the drainage tube were shorter in EN with MCT versus TPN (P = .003), and the length of hospital stay was shorter (P = .032). There were no significant differences between the 2 groups in time from admission to surgery, postoperative days before diagnosing chylothorax, or length of PICU stay (P > .05). CONCLUSIONS: The therapeutic effects of EN with MCT were significantly better than those of TPN, with lower costs. Therefore, we suggest that EN with MCT be chosen first to treat chylothorax caused by surgery with mild chest drainage volume when gastrointestinal tract function is allowed.

Dose-response meta-analysis of coffee consumption and risk of colorectal adenoma.

BACKGROUND: The association between coffee and colorectal adenoma risk remains controversial. We conducted a meta-analysis of cohort and case-control studies to sum up the existing proof about this matter. METHODS: We searched Pubmed, Medline, and Embase for studies published before 1 September 2018 on coffee consumption and colorectal adenoma in any language. The different ORs were calculated for cohort and case-control studies in this study, and we use a random-effects model to aggregate the relative risks of individual studies and conduct dose response, heterogeneity, and publication bias. RESULTS: A total of 8 studies (6 case-control studies, 2 cohort studies) were identified, including 7090 subjects. In a summary analysis of all studies, high coffee intake (compared the highest with the lowest categories) was associated with a reduced risk of colorectal adenoma (odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.55-0.90). The results of subgroup analysis of adenoma location were similar with the pooled analysis, except for rectal adenoma. In the dose-response meta-analysis study, the estimated total odds ratio for increasing coffee consumption by 150 ml per day (about one cup) was 0.91 (95% CI = 0.87-0.95). CONCLUSIONS: The meta-analysis demonstrates possible evidence that increased coffee intake is related to a reduced risk of colon adenoma. However, because of latent confusion and different exposure classification, this finding should be carefully considered.

Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy for Super Super Obese and Super Obese: Systematic Review and Meta-analysis of Weight Results, Comorbidity Resolution.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) used for super obesity (SO) and super super obesity (SSO) remain controversial. The meta-analysis was to summarize the evidence. METHODS: We searched in MEDLINE and PubMed for studies concerning RYGB and SG for SO or SSO and pooled complication, percentage excess weight loss (%EWL), and resolution of comorbidities. RESULTS: Twelve studies were identified. RYGB achieved higher %EWL at 12 months, but no significant difference at 24 months. Resolution of diabetes mellitus and dyslipidemia reached a statistical significance; however, there was no significant difference in hypertension. CONCLUSIONS: RYGB was superior in %EWL for SSO and SO at 12 months. However, regarding at 24 months, RYGB was equal to SG, which is from a meta-analysis and cannot be seen as a definitive conclusion.