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Amorphous solid dispersion (ASD) is an enabling approach utilized to deliver poorly soluble compounds. ASDs can spontaneously generate drug-rich amorphous nanoparticles upon dissolution, which can act as a reservoir for maintaining supersaturation during oral absorption. But, conventional ASDs are often limited in drug loadings to < 20 %. For indications where the dose is high, this can translate into a significant pill burden. The aim of this research was to develop a high drug loading (DL) amorphous nanoparticle (ANP) formulation that can release the drug-rich nanoparticles into solution upon contact with aqueous environment. Nanoparticles were directly engineered using solvent/anti-solvent precipitation. The obtained nanoparticle suspension was then concentrated followed by solidification to a re-dispersible amorphous dosage form using spray drying or lyophilization. The impact of process variables was studied using dynamic light scattering (DLS), scanning electron microscopy (SEM), high performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC). It was observed that spray drying led to a non-re-dispersible formulation. Sucrose and trehalose containing lyocakes resulted in re-dispersible formulations. The trehalose containing lyocakes, in a dog study, gave comparable performance to the reference tablet in the fasted state but lower area under the curve (AUC) in fed state., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AbbVie sponsored and funded the study; contributed to the design; participated in collection, analysis, and interpretation of data; and in writing, reviewing, and approval of the final version. Hitesh S. Purohit, Mengqi Yu, Hardeep Oberoi, Angélica de L Rodríguez López, Manish Kelkar, Yan He, Bradley Gates, Nandkishor Nere, Devalina Law are AbbVie employees and may own AbbVie stock. Maryam Zaroudi contributed to the research during her summer internship at AbbVie. Deliang Zhou contributed to the research during his employment at AbbVie., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Chimeric antigen receptor (CAR) T cell therapy has resulted in positive effects on patients with hematologic malignancy but shows limited efficacy in solid tumor treatments due to insufficient trafficking and tumor infiltration, intensive CAR-T-related toxicities, and antigen escape. In this work, we developed and investigated a biodegradable and biocompatible polymeric toroidal-spiral particle (TSP) as a in vivo cell incubator and delivery device that can be implanted near tumor through a minimally invasive procedure or injected near or into solid tumors by using a biopsy needle. The main matrix structure of the millimeter-sized TSP is made from crosslinking of gelatin methacrylamine (GelMA) and poly (ethylene glycol) diacrylate (PEGDA) with a tunable degradation rate from a few days to months, providing appropriate mechanical properties and sustained release of co-encapsulated drugs and/or stimulation compounds. The toroidal-spiral layer of the particles, presenting an internal void volume for high-capacity cell loading and flexibility of co-encapsulating small and large molecular compounds with individually manipulated release schedules, is filled with collagen and suspended T cells. The TSPs promote cell proliferation, activation, and migration in the tumor micro-environment in a prolonged and sustained manner. In this study, the efficacy of mesothelin (MSLN) CAR-T cells released from the TSPs was tested in preclinical mouse tumor models. Compared to systemic and intratumoral injection, peritumoral delivery of MSLN CAR-T cells using the TSPs resulted in a superior antitumor effect. The TSPs made of FDA approved materials as an in vivo reactor may provide an option for efficiently local delivery of CAR-T cells to solid tumors for higher efficacy and lower toxicity, with a minimally invasive administration procedure., Competing Interests: Declaration of Competing Interest A US patent has been filed by the University of Illinois Chicago, Application number: 63/073,382 filed on Aug. 29, 2021. In situ Cell Bioreactor and Delivery System and Methods of Using the Same. Ying Liu., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Currently, there is no consensus on the optimal vitamin D administration in bariatric patients. The present systematic review and meta-analysis were conducted to examine the effect of vitamin D supplements on serum level of 25(OH) vitamin D in the patients undergoing bariatric surgery (BS).Random model effects were used to estimate standardized mean difference (SMD) with a 95% confidence interval (CI). Nine clinical trials were included in the meta-analysis. Vitamin D supplementation in patients undergoing BS modestly improves vitamin D status (SMD, 0.53; 95% CI, 0.28, 0.77) particularly, in the dosages above 2850 IU/day and in the patients with BMI greater than 50 kg/m 2 . Vitamin D supplementation was associated with prevention of raising of the PTH serum concentration and without impact on serum calcium levels., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background & Aims: Cardamom known as "queen of spice" seems to be an anti-diabetic agent due to its poly phenolic content. Since, recent studies reported controversial results related to its effect on metabolic factors, present meta-analysis examined the effect of cardamom supplementation on glycemic indices and weight profile of randomized controlled clinical trials (RCTs)., Methods: A wide search was done on biomedical electronic databases including Scopus, PubMed, Cochrane, EMBASE and Iranian databases, for all relevant literature published up to May 2021. Our search strategy included: [HbA1C, Blood Sugar, glycemic index, glucose tolerance test, insulin, insulin resistance, insulin sensitivity, body weight, BMI, body composition, waist circumferences] added to searched queries based on scientific Mesh terms. The included papers required to be RCTs that reported the effect of cardamom on glycemic and weight indices. We excluded studies with: a) non-randomized or non-controlled trials, b) animal studies, c) not available full text articles d) duplicate citations and e) not available full text articles. The risk of bias was assessed based on the Cochrane Risk of Bias tool. The effects of cardamom supplementation were assessed using standardized mean difference (SMD) statistics. The SMD of metabolic risk factors were pooled together using random effect meta-analysis method., Results: Totally, six publications enrolling 410 participants was included in present meta-analysis. Daily 3 g supplementation of cardamom from 8 weeks to 3 months showed no significant effect on BMI (WMD: 0.07; 95% CI: [-0.12, 0.27]; P:0.5), weight (WMD: 0.01; 95% CI: [-0.22, 0.21]; P:0.95) and WC (WMD: 0.09; 95% CI: [-0.34, 0.17]; P:0.63), FBS (WMD: 0.10; 95% CI: [ -0.32, 0.12]; P:0.37), insulin (WMD: 0.83; 95% CI: [-2.07, 0.40]; P:0.19) and QUICKI (WMD: 1.14; 95% CI: [-1.11, 3.39]; P:0.32). However, significant effect occurred on HOMA-IR (WMD: 0.40; 95% CI: [-0.65, -0.15]; P:0.00), and HbA1C (WMD: 0.48; 95% CI: [-0.80, -0.16]; P:0.00)., Conclusion: Final findings suggest ameliorative effect of cardamom on metabolism of glucose., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Transplantable cell encapsulation systems present a promising approach to deliver a therapeutic solution from hormone-producing cells for the treatment of endocrine diseases like type 1 diabetes. However, the development of a broadly effective and safe transplantation system has been challenging. While some current micro-sized capsules have been optimized for adequate nutrient and metabolic transport, they lack the robustness and retrievability for the clinical safety translation that macro-devices may offer. An existing challenge to be addressed in the current macro-devices is their configuration which may lead to unsatisfactory mass transfer. Here, we design and characterize a millimeter-size particle system of poly-ethylene glycol (PEG) featuring internal toroidal spiral channels, called toroidal spiral particles (TSPs). The characteristic internal structure of the TSPs allows for large encapsulation capacity and large surface area available to all the encapsulated cell mass for effective molecular diffusion. The polymeric matrix renders the particle flexible yet robust for safe transplantation and retrieval. We demonstrate the feasibility of fabricating these particles with various polymer compositions, while optimizing their mechanical properties as well as glucose and insulin permeability. Encapsulation of islets of Langerhans is achieved with high loading capacity (∼160 IEQ per TSP) and excellent cell viability. TSP-encapsulated islets showed similar glucose-stimulated insulin secretion to the naked islets. Preliminary biocompatibility of the TSPs on naïve C57BL/6 mice shows minimal inflammatory response after 4-week transplantation into the intraperitoneal (IP) space. Long-term therapeutic efficacy of encapsulated islets needs to be confirmed in diabetic rodent models in the future, while determining minimal mass required to reverse diabetes. However, we believe from the in vitro favorable results and the TSPs' unique design that TSPs may provide a safe, effective method to transplant and retrieve therapeutic cells for type 1 diabetes treatment and may also be applicable for other cell therapies.

We report a particulate cell delivery platform, toroidal spiral particles (TSPs), for continuous cell activation, expansion, and local sustained release. Biocompatible TSPs, generated by a self-assembly process of polymeric droplet sedimentation in an aqueous solution and subsequent polymer solidification, possess many engineering design flexibilities to manipulate the microenvironment of the cells to control cell proliferation, migration, and release kinetics. These millimeter-size particles with desired mechanical and physicochemical properties may be potentially used for adoptive cellular therapy (ACT) delivery by a minimally invasive procedure to the tumor mass.

Objective: This study evaluated the effects of melatonin supplementation on parameters of mental health, glycemic control, markers of cardiometabolic risk, and oxidative stress in diabetic hemodialysis (HD) patients., Design: A randomized, double-blind, placebo-controlled clinical trial was conducted in 60 diabetic HD patients, 18-80 years of age. Participants were randomly divided into 2 groups to take either melatonin (2 x 5mg/day) (n = 30) or placebo (n = 30) 1 hour before bedtime for 12 weeks. The effects of melatonin on mental health, metabolic status, and gene expression related to metabolic status were assessed using multiple linear regression adjusting for age and BMI., Results: Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (P = .007), Beck Depression Inventory index (P = .001), and Beck Anxiety Inventory index (P = .01) compared with the placebo. Additionally, melatonin administration significantly reduced fasting plasma glucose (β = -21.77 mg/dL, 95% CI -33.22 to -10.33, P < .001), serum insulin levels (β = -1.89 μIU/mL, 95% CI -3.34 to -0.45, P = .01), and homeostasis model of assessment-insulin resistance (β = -1.45, 95% CI -2.10 to -0.80, P < .001), and significantly increased the quantitative insulin sensitivity check index (β = 0.01, 95% CI 0.007-0.02, P < .001) compared with placebo treated subjects. In addition, melatonin administration resulted in a significant reduction in serum high sensitivity C-reactive protein (β = -1.92 mg/L, 95% CI -3.02 to -0.83, P = .001) and plasma malondialdehyde (β = -0.21 μmol/L, 95% CI -0.36 to -0.06, P = .005); also, significant rises in plasma total antioxidant capacity (β = 253.87 mmol/L, 95% CI 189.18-318.56, P < .001) and nitric oxide levels (β = 2.99 μmol/L, 95% CI 0.71-5.28, P = .01) were observed compared with the placebo., Conclusion: Overall, melatonin supplementation for 12 weeks to diabetic HD patients had beneficial effects on mental health, glycemic control, inflammatory markers, and oxidative stress., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Cervical cancer is the fourth-ranked cancer in the world and is associated with a large number of deaths annually. Chemotherapy and radiotherapy are known as the common therapeutic approaches in the treatment of cervical cancer, but because of their side effects and toxicity, researchers are trying to discovery alternative therapies. Beta-glucans, a group of glucose polymers that are derived from the cell wall of fungi, bacteria, and etc. it has been showed that beta-glucans have some anti-cancer properties which due to their impacts on adaptive and innate immunity. Along to these impacts, these molecules could be used as drug carriers. In this regard, the application of beta-glucans is a promising therapeutic option for the cancer prevention and treatment especially for cervical cancer. Herein, we have summarized the therapeutic potential of beta-glucans alone or as adjuvant therapy in the treatment of cervical cancer. Moreover, we highlighted beta-glucans as drug carriers for preventive and therapeutic purposes.

Background: In the current meta-analysis of randomized controlled trials (RCTs), the effects of vitamin D supplementation on mental health, and biomarkers of inflammation and oxidative stress in patients with psychiatric disorders are assessed., Methods: The following databases were search up to March 2019: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The quality of the relevant extracted data was assessed according to the Cochrane risk of bias tool. Data were pooled by the use of the inverse variance method and expressed as mean difference with 95% Confidence Intervals (95% CI)., Results: Eleven effect sizes from nine studies were included in the final analyses. A pooled analysis of 9 effect sizes showed a significant reduction in Beck Depression Inventory (BDI) score following supplementation with vitamin D [weighted mean difference (WMD): -3.91; 95% CI: -5.15 -2.66), I 2 = 85.9%]. Combining data from two available studies on the effects of vitamin D supplementation on Pittsburgh Sleep Quality Index (PSQI) also revealed a significant reduction in this score following the intervention (WMD: -1.78; 95% CI: -2.28, -1.28). In addition, there were significant increase in glutathione (GSH) through 3 studies (WMD: 180.70; 95% CI: 6.76, 354.64), and in total antioxidant capacity (TAC) through 3 studies (WMD: 90.09; 95% CI: 56.36, 123.82) after vitamin D supplementation. Combining data from five studies, we found a significant reduction in C-reactive protein (CRP) concentrations after vitamin D supplementation (WMD: -1.74; 95% CI: -2.82, -0.66)., Conclusions: Overall, the current meta-analysis demonstrated that taking vitamin D supplements among patients with psychiatric disorders had beneficial effects on BDI, PSQI, GSH, TAC and CRP levels, but did not affect other biomarkers of inflammation and oxidative stress., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Most studies that have evaluated the association between combined lifestyle factors and mortality outcomes have been conducted in populations of developed countries., Objectives: The aim of this study was to examine the association between combined lifestyle scores and risk of all-cause and cause-specific mortality for the first time among Iranian adults., Methods: The study population included 50,045 Iranians, 40 - 75 years of age, who were enrolled in the Golestan Cohort Study, between 2004 and 2008. The lifestyle risk factors used in this study included cigarette smoking, physical inactivity, and Alternative Healthy Eating Index. The lifestyle score ranged from zero (non-healthy) to 3 (most healthy) points. From the study baseline up to analysis, a total of 4691 mortality cases were recorded. Participants with chronic diseases at baseline, outlier reports of calorie intake, missing data, and body mass index of less than 18.5 were excluded from the analyses. Cox regression models were fitted to establish the association between combined lifestyle scores and mortality outcomes., Results: After implementing the exclusion criteria, data from 40,708 participants were included in analyses. During 8.08 years of follow-up, 3,039 cases of all-cause mortality were recorded. The adjusted hazard ratio of a healthy lifestyle score, compared with non-healthy lifestyle score, was 0.68 (95% CI: 0.54, 0.86) for all-cause mortality, 0.53 (95% CI: 0.37, 0.77) for cardiovascular mortality, and 0.82 (95% CI: 0.53, 1.26) for mortality due to cancer. When we excluded the first two years of follow up from the analysis, the protective association between healthy lifestyle score and cardiovascular death did not change much 0.55 (95% CI: 0.36, 0.84), but the inverse association with all-cause mortality became weaker 0.72 (95% CI: 0.55, 0.94), and the association with cancer mortality was non-significant 0.92 (95% CI: 0.58, 1.48). In the gender-stratified analysis, we found an inverse strong association between adherence to healthy lifestyle and mortality from all causes and cardiovascular disease in either gender, but no significant relationship was seen with mortality from cancer in men or women. Stratified analysis of BMI status revealed an inverse significant association between adherence to healthy lifestyle and mortality from all causes, cardiovascular disease and cancer among non-obese participants., Conclusion: We found evidence indicating that adherence to a healthy lifestyle, compared to non-healthy lifestyle, was associated with decreased risk of all-cause mortality and mortality from cardiovascular diseases in Iranian adults.

Objective: We aimed to assess the relationship between major dietary patterns and risk of diabetes type 2 among Iranian adults., Methods: In this population-based case-control study in Mazandaran province, we enrolled 332 subjects (110 newly diagnosed cases and 222 controls) aged 43 - 77 years. Dietary intakes were collected using a validated semi-quantitative food frequency questionnaire (FFQ). Data on demographic, anthropometric, socioeconomic characteristics and other covariates were collected using structured lifestyle questionnaires. Factor analysis was used to identify major dietary patterns. Odds ratios (OR) were calculated for risk of type 2 diabetes across quartiles of dietary pattern scores., Results: Three major dietary patterns were identified, including: "healthy", "transitional" and "traditional". A significant direct association was found between the transitional dietary pattern and risk of diabetes type 2 after adjustment of potential confounders (OR = 2.17; 95% CI: 1.0, 4.50; Ptrend = 0.02). The traditional dietary pattern was significantly associated with the increased risk of diabetes type 2 after controlling for confounders (OR = 2.13; 95% CI: 1.03, 4.41; Ptrend = 0.01). There was no significant relationship between healthy dietary pattern and risk of diabetes type 2., Conclusions: In conclusion, transitional dietary pattern characterized by high consumption of salt, organ meats, dried fruits, poultry, tea, low- fat dairy and other vegetables. Traditional dietary pattern characterized by high intakes of garlic, dough, high- fat dairy, dried fruits, red meats, grains, as well as animal and hydrogenated fats were associated with an increased risk of type 2 diabetes. No significant associations were found between the healthy dietary pattern and risk of diabetes type 2.