Immune checkpoint inhibition for the treatment of cancers: An update and critical review of ongoing clinical trials.

Advances in Cancer immunotherapy in the past few years include the development of medications that modulate immune checkpoint proteins. Cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death protein 1 (PD1), and programmed cell death ligand 1 (PD-L1) are three co-inhibitory receptors that are expressed in the tumor microenvironment. Immune checkpoint inhibitors (ICI) that target these biomarkers unleash the properties of effector T cells that are licensed to kill cancer cells. Immune checkpoint blockade has dramatically changed the treatment landscape of many cancers. In this Review, we describe the current data regarding clinical trials of ICIs in six important cancers, including hepatocellular carcinoma (HCC), renal cell cancer (RCC), hodgkin lymphoma (HL), non-hodgkin lymphoma (NHL), non-small cell lung cancer (NSCLC), and head and neck cancer carcinoma (HNSCC).

An improved method in fabrication of smart dual-responsive nanogels for controlled release of doxorubicin and curcumin in HT-29 colon cancer cells.

The combination therapy which has been proposed as the strategy for the cancer treatment could achieve a synergistic effect for cancer therapies and reduce the dosage of the applied drugs. On account of the the unique properties as the high absorbed water content, biocompatibility, and flexibility, the targeting nanogels have been considred as a suitable platform. Herein, a non-toxic pH/thermo-responsive hydrogel P(NIPAAm-co-DMAEMA) was synthesized and characterized through the free-radical polymerization and expanded upon an easy process for the preparation of the smart responsive nanogels; that is, the nanogels were used for the efficient and controlled delivery of the anti-cancer drug doxorubicin (DOX) and chemosensitizer curcumin (CUR) simultaneously like a promising strategy for the cancer treatment. The size of the nanogels, which were made, was about 70 nm which is relatively optimal for the enhanced permeability and retention (EPR) effects. The DOX and CUR co-loaded nanocarriers were prepared by the high encapsulation efficiency (EE). It is important to mention that the controlled drug release behavior of the nanocarriers was also investigated. An enhanced ability of DOX and CUR-loaded nanoformulation to induce the cell apoptosis in the HT-29 colon cancer cells which represented the greater antitumor efficacy than the single-drug formulations or free drugs was resulted through the In vitro cytotoxicity. Overall, according to the data, the simultaneous delivery of the dual drugs through the fabricated nanogels could synergistically potentiate the antitumor effects on the colon cancer (CC).

Vitamin D Supplementation Affects the Beck Depression Inventory, Insulin Resistance, and Biomarkers of Oxidative Stress in Patients with Major Depressive Disorder: A Randomized, Controlled Clinical Trial.

BACKGROUND: Vitamin D may decrease depression symptoms through its beneficial effects on neurotransmitters, metabolic profiles, biomarkers of inflammation, and oxidative stress. OBJECTIVE: This study was designed to assess whether vitamin D supplementation can reduce symptoms of depression, metabolic profiles, serum high-sensitivity C-reactive protein (hs-CRP), and biomarkers of oxidative stress in patients with major depressive disorder (MDD). METHODS: This randomized, double-blind, placebo-controlled clinical trial was performed in 40 patients between 18 and 65 y of age with a diagnosis of MDD based on criteria from the Diagnostic and Statistical Manual of Mental Disorders. Patients were randomly assigned to receive either a single capsule of 50 kIU vitamin D/wk (n = 20) or placebo (n = 20) for 8 wk. Fasting blood samples were taken at baseline and postintervention to quantify relevant variables. The primary [Beck Depression Inventory (BDI), which examines depressive symptoms] and secondary (glucose homeostasis variables, lipid profiles, hs-CRP, and biomarkers of oxidative stress) outcomes were assessed. RESULTS: Baseline concentrations of mean serum 25-hydroxyvitamin D were significantly different between the 2 groups (9.2 ± 6.0 and 13.6 ± 7.9 µg/L in the placebo and control groups, respectively, P = 0.02). After 8 wk of intervention, changes in serum 25-hydroxyvitamin D concentrations were significantly greater in the vitamin D group (+20.4 µg/L) than in the placebo group (-0.9 µg/L, P < 0.001). A trend toward a greater decrease in the BDI was observed in the vitamin D group than in the placebo group (-8.0 and -3.3, respectively, P = 0.06). Changes in serum insulin (-3.6 compared with +2.9 µIU/mL, P = 0.02), estimated homeostasis model assessment of insulin resistance (-1.0 compared with +0.6, P = 0.01), estimated homeostasis model assessment of ß cell function (-13.9 compared with +10.3, P = 0.03), plasma total antioxidant capacity (+63.1 compared with -23.4 mmol/L, P = 0.04), and glutathione (+170 compared with -213 µmol/L, P = 0.04) in the vitamin D group were significantly different from those in the placebo group. CONCLUSION: Overall, vitamin D supplementation of patients with MDD for 8 wk had beneficial effects on the BDI, indicators of glucose homeostasis, and oxidative stress. This trial was registered at www.irct.ir as IRCT201412065623N29.

Effects of daily consumption of synbiotic bread on insulin metabolism and serum high-sensitivity C-reactive protein among diabetic patients: a double-blind, randomized, controlled clinical trial.

BACKGROUND: This study was conducted to evaluate the effects of daily consumption of synbiotic bread on the metabolic status of patients with type 2 diabetes mellitus. METHODS: This randomized, double-blind, controlled clinical trial was performed in 81 diabetic patients. The subjects were randomly assigned to consumption of synbiotic (n = 27), probiotic (n = 27), or control bread (n = 27) for 8 weeks 3 times a day in a 40-gram package. The synbiotic bread contained Lactobacillus sporogenes (1 × 10(8) CFU) and 0.07 g inulin per 1 g. The probiotic bread contained L. sporogenes (1 × 10(8) CFU per 1 g). Fasting blood samples were taken at baseline and after an 8-week intervention for quantification of related factors. RESULTS: Consumption of the synbiotic bread resulted in a significant reduction in serum insulin levels (-3.2 ± 5.4 vs. -0.3 ± 3.4 and 0.6 ± 4.7 µIU/ml, respectively, p = 0.007), homeostatic model assessment for insulin resistance scores (-1.5 ± 2.7 vs. -0.2 ± 1.6 and 0.4 ± 3.5, respectively, p = 0.03), and homeostatic model assessment-ß-cell function (-7.2 ± 16.3 vs. -0.7 ± 10.8 and 0.7 ± 8.2, respectively, p = 0.04) compared to the probiotic and control breads. We did not find any significant effect of synbiotic bread consumption on fasting plasma glucose, the quantitative insulin sensitivity check index, or serum hs-CRP levels compared to other breads. CONCLUSION: Consumption of the synbiotic bread among diabetic patients had beneficial effects on insulin metabolism.

Effect of some hydrocolloids blend on viscosity and sensory properties of raspberry juice-milk.

Raspberry juice-milk is an acidic dairy drink (ADD) including two main phases, milk phase (pH: 6.6-6.7) and raspberry juice phase (pH: 3.2 ± 0.1). Due to the low pH in this beverage, milk protein sedimentation is usual problem and therefore hydrocolloid is added as a stabilizer. Thus, in current study the influences of pectin, CMC and Kappa-carrageenan on the stability of the milk-raspberry juice drink and their blend synergistic effect were investigated. For this purpose milk-raspberry juice drink samples were prepared using pure pectin, CMC and Kappa-carrageenan at concentrations of 0.2 %, 0.3 % and 0.35 % respectively. Blends of pectin and Carboxymethylcellulose (ratios of 25:75, 33.4:66.6 and 34.3:65.7) at concentrations of 0.2 %, 0.3 % and 0.35 %, were added during a certain process. Moreover, the stabilization mechanisms were studied using apparent viscosity and sedimentation percent measurements. Based on the findings of the present study, the best fitted samples were the ones containing the blends of pectin and Carboxymethylcellulose which were more stable and viscose than samples including pure Carboxymethylcellulose (P < 0.05). Kappa-carrageenan can not prevent casein agglomeration in raspberry juice-milk individually, but in the presence of CMC or CMC and pectin it produces a stable drink. In general, with utilizing synergistic effect of gum blend we can use lower gum concentration and decrease cost during manufacture.

Folate receptor-mediated delivery system based on chitosan coated polymeric nanoparticles for combination therapy of breast cancer.

Combination therapy using two or more drugs with different mechanisms of action is an effective strategy for treating cancer. This is because of the synergistic effect of complementary drugs that enhances their effectiveness. However, this approach has some limitations, such as non-specific distribution of the drugs in the tumor and the occurrence of dose-dependent toxicity to healthy tissues. To overcome these issues, we have developed a folate receptor-mediated co-delivery system that improves the access of chemotherapy drugs to the tumor site. We prepared a nanoplatform by encapsulating paclitaxel (PTX) and curcumin (CUR) in poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone) (PCL-PEG-PCL) co-polymer using a double emulsion method and coating nanoparticles with pH-responsive chitosan-folic acid (CS-FA) conjugate. The nanocarrier's physicochemical properties were studied, confirming successful preparation with appropriate size and morphology. PTX and CUR could be released synchronously in a controlled and acid-facilitated manner. The dual drug-loaded nanocarrier exhibited excellent anti-tumor efficiency in MDA-MB-231 cells in vitro. The active targeting effect of FA concluded from the high inhibitory effect of dual drug-loaded nanocarrier on MDA-MB-231 cells, which have overexpressed folate receptors on their surface, compared to Human umbilical vein endothelial cells (HUVEC). Overall, the nanoengineered folate receptor-mediated co-delivery system provides great potential for safe and effective cancer therapy.

Thermo- and pH-sensitive dendrosomes as bi-phase drug delivery systems.

Fully supramolecular dendrosomes (FSD) as bi-phase drug delivery systems are reported in this work. For preparation of FSD, amphiphilic linear-dendritic supramolecular systems (ALDSS) have been synthesized by host-guest interactions between hyperbranched polyglycerol having ß-cyclodextrin core and bi-chain polycaprolactone (BPCL) with a fluorescine focal point. Self-assembly of ALDSS in aqueous solutions led to FSD. They were able to encapsulate paclitaxel with a high loading capacity. The dendrosome-based drug delivery systems were highly sensitive to pH and temperature. They were stable at 20-37 °C and pH7-8, but dissociated and released drug at temperatures lower than 20 °C or higher than 37 °C and pH lower than 7 quickly. Dissociation of FSD building blocks by temperature or pH resulted in inclusion complexes between the released drugs and polyglycerol as the secondary drug delivery system. FROM THE CLINICAL EDITOR: This paper reports on the development of a pH- (below 7) and temperature- (below 20 °C or above 37 °C) sensitive delivery system using supramolecular dendrosomes for more specific delivery and release of drugs using paclitaxel as a model.

An efficient method for cell sheet bioengineering from rBMSCs on thermo-responsive PCL-PEG-PCL copolymer.

Utilizing both medium enrichment and a thermos-responsive substrate to maintain the cell-to-cell junctions and extracellular matrix (ECM) intact, cell sheet technology has emerged as a ground-breaking approach. Investigating the possibility of using sodium selenite (as medium supplementation) and PCL-PEG-PCL (as vessel coating substrate) in the formation of the sheets from rat bone marrow-derived mesenchymal stem cells (rBMSCs) was the main goal of the present study. To this end, first, Polycaprolactone-co-Poly (ethylene glycol)-co-Polycaprolactone triblock copolymer (PCEC) was prepared by ring-opening copolymerization method and characterized by FTIR, 1 H NMR, and GPC. The sol-gel-sol phase transition temperature of the PCEC aqueous solutions with various concentrations was either measured. Next, rBMSCs were cultured on the PCEC, and let be expanded in five different media containing vitamin C (50 µg/ml), sodium selenite (0.1 µM), vitamin C and sodium selenite (50 µg/ml + 0.1 µM), Trolox, and routine medium. The proliferation of the cells exposed to each material was evaluated. Produced cell sheets were harvested from the polymer surface by temperature reduction and phenotypically analyzed via an inverted microscope, hematoxylin and eosin (H&E) staining, and field emission scanning electron microscopy (FESEM). Through the molecular level, the expression of the stemness-related genes (Sox2, Oct-4, Nanog), selenium-dependent enzymes (TRX, GPX-1), and aging regulator gene (Sirt1) were measured by q RT-PCR. Senescence in cell sheets was checked by beta-galactosidase assay. The results declared the improved ability of the rBMSCs for osteogenesis and adipogenesis in the presence of antioxidants vitamin C, sodium selenite, and Trolox in growth media. The data indicated that in the presence of vitamin C and sodium selenite, the quality of the cell sheet was risen by reducing the number of senescent cells and high transcription of the stemness genes. Monolayers produced by sodium selenite was in higher-quality than the ones produced by vitamin C.

Synthesis and characterization of growth factor free nanoengineered bioactive scaffolds for bone tissue engineering.

BACKGROUND: To address the obstacles that come with orthopedic surgery for biological graft tissues, including immune rejections, bacterial infections, and weak osseointegration, bioactive nanocomposites have been used as an alternative for bone grafting since they can mimic the biological and mechanical properties of the native bone. Among them, PCL-PEG-PCL (PCEC) copolymer has gained much attention for bone tissue engineering as a result of its biocompatibility and ability for osteogenesis. METHODS: Here, we designed a growth factor-free nanoengineered scaffold based on the incorporation of Fe3O4 and hydroxyapatite (HA) nanoparticles into the PCL-PEG-PCL/Gelatin (PCEC/Gel) nanocomposite. We characterized different formulations of nanocomposite scaffolds in terms of physicochemical properties. Also, the mechanical property and specific surface area of the prepared scaffolds, as well as their feasibility for human dental pulp stem cells (hDPSCs) adhesion were assessed. RESULTS: The results of in vitro cell culture study revealed that the PCEC/Gel Fe3O4&HA scaffold could promote osteogenesis in comparison with the bare scaffold, which confirmed the positive effect of the Fe3O4 and HA nanoparticles in the osteogenic differentiation of hDPSCs. CONCLUSION: The incorporation of Fe3O4 and HA with PCEC/gelatin could enhance osteogenic differentiation of hDPSCs for possible substitution of bone grafting tissue.

The fabrication of halloysite nanotube-based multicomponent hydrogel scaffolds for bone healing.

Bone tissue engineering, as an alternative for common available therapeutic approaches, has been developed to focus on reconstructing of the missing tissues and restoring their functionality. In this work, three-dimensional (3D) nanocomposite scaffolds of polycaprolactone-polyethylene glycol-polycaprolactone/gelatin (PCEC/Gel) were prepared by freeze-drying method. Biocompatible nanohydroxyapatite (nHA), iron oxide nanoparticle (Fe3O4) and halloysite nanotube (HNT) powders were added to the polymer matrix aiming to combine the osteogenic activity of nHA or Fe3O4 with high mechanical strength of HNT. The scanning electron microscope (SEM) methods was utilized to characterize the nanotube morphology of HNT as well as nanoparticles of Fe3O4 and nHA. Prepared scaffolds were characterized via Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), and SEM methods. In addition, the physical behavior of scaffolds was evaluated to explore the influence of HNT on the physicochemical properties of composites. Cell viability and attachment were investigated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay and SEM on human dental pulp-derived mesenchymal stem cells (h-DPSCs) in-vitro. Cell proliferation was observed without any cytotoxicity effect on h-DPSCs for all examined scaffolds. Alizarin red (ARS) and alkaline phosphatase (ALP) staining were carried out to determine the osteoconductivity of scaffolds. The data demonstrated that all PCEC/Gel/HNT hydrogel scaffolds supported osteoblast differentiation of hDPSCs with moderate effects on cell proliferation. Moreover, PCEC/Gel/HNT/nHA with proper mechanical strength showed better biological activity compared to PCEC/Gel/HNT/Fe3O4 and PCEC/Gel/HNT scaffolds. Therefore, this study suggested that with proper fillers content, PCEC/Gel/HNT nanocomposite hydrogels alone or in a complex with nHA, Fe3O4 could be a suitable candidate for hard tissue regeneration.

Gentamycin-loaded halloysite-based hydrogel nanocomposites for bone tissue regeneration: fabrication, evaluation of the antibacterial activity and cell response.

Biocompatible hydrogels are promising approaches for bone repair and engineering. A novel therapeutic nanocomposite hydrogel was designed based on triblock copolymer poly e-caprolactone (PCL)-polyethylene glycol-PCL and natural gelatin (PCEC/GEL) and reinforced with halloysite nanotube (HNT). Gentamicin (GM) loaded HNT was immobilized in polymeric hydrogel matrix to fabricate scaffolds using the freeze-drying method. Scaffolds were characterized via Fourier transform infrared (FT-IR), x-ray powder diffraction, and scanning electron microscope (SEM) methods. The swelling ratio, density, porosity, degradation, and mechanical behavior were evaluated to investigate the effects of HNT on the physicochemical properties of the composite. Cell viability and cell attachment were investigated by microculture tetrazolium (MTT) assay and SEM. Cell proliferation was observed without any cytotoxicity effect on human dental pulp-derived mesenchymal stem cells (h-DPSCs). Alizarin red staining and real-time reverse transcription polymerase chain reaction (QRT-PCR) assay were carried out to monitor the osteoconductivity of scaffolds on h-DPSCs which were seeded drop wise onto the top of scaffolds. The quantification of the messenger RNA (mRNA) expression of osteogenic marker genes, bone morphogenetic protein 2, SPARK, bone gamma-carboxyglutamate protein and runt-related transcription factor 2 over a period of 21 d of cell seeding, demonstrated that cell-encapsulating PCEC/GEL/HNT-GM hydrogel scaffolds supported osteoblast differentiation of h-DPSCs into osteogenic cells through the up-regulation of related genes along with moderate effects on cell viability. Moreover, the antibiotics loading reduced bacterial growth while maintaining the osteogenic properties of the scaffold. Therefore, the bactericidal PCEC/GEL/HNT-GM hydrogel nanocomposite, with enhanced durability, maintenance the functionality of seeded cellsin vitrothat can be a remarkable dual-functional candidate for hard tissue reconstruction and customized bone implants fabrication via the direct incorporation of bactericidal drug to prevent infection.

Coronary pseudoaneurysm 1 week after complex percutaneous coronary intervention with drug-eluting stent.

Pseudoaneurysm formation is a rare complication after complex PCI with drug-eluting stents. Cardiologists and interventionist should be familiar with this rare complication after PCI and its management options.

Lysine-embedded cellulose-based nanosystem for efficient dual-delivery of chemotherapeutics in combination cancer therapy.

Combination therapy by two or multiple drugs with different mechanisms of action is a promising strategy in cancer treatment. In this regard, a wide range of chemotherapeutics has used simultaneously to achieve the synergistic effect and overcome the adverse side effects of single-drug therapy. Herein, we developed a biocompatible nanoparticle-based system composed of nanocrystalline cellulose (NCC) and amino acid l-lysine for efficient co-delivery of model chemotherapeutic methotrexate (MTX) and polyphenol compound curcumin (CUR) to the MCF-7 and MDA-MB-231 cells. The drugs could release in a sustained and acidic-facilitate manner. In vitro cytotoxicity results represented the superior anti-tumor efficacy of the dual-drug-loaded nanocarriers. Possible inhibition of cell growth and induction of apoptosis in the cells treated with different formulations of CUR and MTX were explored by cell cycle analysis and DAPI staining. Overall, the engineered nanosystem can be used as suitable candidates to achieve efficient multi-drug delivery for combination cancer therapy.

Evaluating two ovarian decellularization methods in three species.

Since there is dearth of practical ways to obtain mature follicles from cryopreserved or native ovarian tissues, especially in patients suffering from ovarian dysfunction, tissue engineering may help in restoring ovarian function and/or fertility. In the present study, the effects of sodium dodecyl sulfate (SDS) and sodium hydroxide (NaOH) on the decellularization of ovarian tissues were studied in order to ascertain their suitability in creating suitable bioscaffolds. Cells were removed from the ovarian tissues of mouse, sheep and human. The samples were distributed among three groups, viz., control (not treated), SDS and NaOH treated. Qualitative histological evaluations, quantitative assessments (nuclear contents, collagen and glycosaminoglycan), immunohistochemistry staining (for laminin, fibronectin and Collagen I), cell viability and scanning electron microscopic (SEM) assays were performed for all experimental groups. Finally, suspensions of mouse ovarian cells were injected into human NaOH treated scaffolds and subsequently auto-transplanted to ovariectomized mice. H&E and IHC staining (GDF-9) were performed on human recellularized NaOH treated scaffolds 1 month after auto-transplantation. Although histological studies and quantitative evaluations confirmed the successful decellularization and presence of key factors in ovarian scaffolds under both treatment methods, NaOH showed more interesting outcomes. Cell metabolic activity in sheep and human ovaries treated with NaOH was statistically (p < 0.05) higher than for SDS treated samples after 72 h. Moreover, spherical associations with cuboidal cells in human NaOH treated scaffolds were observed and this follicular reconstruction was also confirmed by GDF-9. NaOH was found to be more suitable than SDS for the decellularization of ovarian tissues and it supports follicular reconstruction better than SDS. This is a valuable finding in tissue engineering research and can help in the creation of appropriate ovarian bioscaffolds.

The effect of tactile-kinesthetic stimulation on growth indices of healthy neonates.

Therapeutic touch is emphasized by healthcare professionals for improvement of neonates' growth and development. However, inconsistencies exist regarding effects and methods of massage in neonates. The purpose of this clinical trial is to assess and comprise intervention and control groups regarding the effects of tactile-kinesthetic stimulation (TKS) by mothers on growth indices of healthy term neonates. Sixty healthy term neonates were randomly assigned into intervention and control groups. Mothers of neonates in the experimental group were trained to perform TKS for their newborns at home before feeding for at least 28 consecutive days, two times a day, and 15 min each time. Neonates in the control group were not required to receive this intervention. The neonates' growth indices were measured within 24 h after birth, and then at days 14 and 28. During the study and the three consecutive measurements, no significant difference was found between the mean weights, heights, and head circumferences of the neonates in the two groups (p > 0.05).

Dental Pulp Response to RetroMTA after Partial Pulpotomy in Permanent Human Teeth.

INTRODUCTION: A lack of information exists regarding the efficacy of RetroMTA (BioMTA, Seoul, Korea) directly applied on the pulp in vital pulp therapy. This study was designed to examine the clinical efficacy of RetroMTA compared with ProRoot mineral trioxide aggregate (MTA) (Dentsply Tulsa Dental, Tulsa, OK) for partial pulpotomy. METHODS: Partial pulpotomy was performed in 22 healthy human maxillary and mandibular third molars planned for extraction. The teeth were randomly divided into 2 groups (n = 11) and underwent partial pulpotomy with RetroMTA and ProRoot MTA as the control. The teeth were then restored with glass ionomer cement. Clinical and electric pulp tests were performed after 1 and 8 weeks. The teeth were radiographed and extracted at 8 weeks. Histologic sections were prepared and analyzed for pulp inflammation and dentinal bridge formation. Data were analyzed using the Mann-Whitney U test. RESULTS: Clinical examination after 1 and 8 weeks showed no sensitivity to heat, cold, or palpation in the ProRoot MTA and RetroMTA groups. Periapical radiographs taken before the extraction of teeth showed no evidence of periapical pathology. Electric pulp testing revealed no sensitivity. Data comparisons using the Mann-Whitney U test showed no significant difference between the materials with regard to the pulp inflammation type, intensity and extension (P = .3), or bridge continuity (P = .12). However, these data revealed a significant difference between the 2 materials in pulp morphology (P < .05) and bridge thickness (P < .01). CONCLUSIONS: This is the first work to evaluate a RetroMTA histologic outcome in partial pulpotomy in human permanent teeth. It shows pulp disorganization, an absence of inflammation, and discontinuous mineralization, which may represent a potential drawback with RetroMTA in this indication.

Human Pulp Responses to Partial Pulpotomy Treatment with TheraCal as Compared with Biodentine and ProRoot MTA: A Clinical Trial.

INTRODUCTION: Questions exist regarding the efficacy of resin-containing materials such as TheraCal directly applied on the pulp. This study sought to investigate the clinical efficacy of TheraCal as compared with Biodentine and ProRoot mineral trioxide aggregate (MTA) for partial pulpotomy. METHODS: In this clinical trial, partial pulpotomy was performed for 27 sound human maxillary and mandibular third molars scheduled for extraction. The teeth were randomly divided into 3 groups (n = 9) and underwent partial pulpotomy with TheraCal, Biodentine, and ProRoot MTA. The teeth were then restored with glass ionomer cement. Clinical and electric pulp tests were performed after 1 and 8 weeks. The teeth were radiographed and extracted at 8 weeks. Histologic sections were prepared and analyzed for pulp inflammation and dentinal bridge formation. Data were analyzed by using one-way analysis of variance. RESULTS: Clinical examination showed no sensitivity to heat, cold, or palpation in ProRoot MTA and Biodentine groups. Two patients in TheraCal group (20%) reported significant pain at 1 week. Periapical radiographs showed no periapical pathology, and electric pulp test revealed a normal pulp response with no hypersensitivity. Inflammation was absent with all materials at 8 weeks. Normal pulp organization was seen in 33.33% of the teeth in ProRoot MTA, 11.11% in TheraCal, and 66.67% in Biodentine group (P = .06). Biodentine group showed complete dentinal bridge formation in all teeth, whereas this rate was 11% and 56% in TheraCal and ProRoot MTA groups, respectively (P = .001). CONCLUSIONS: Overall, Biodentine and MTA performed better than TheraCal when used as partial pulpotomy agent and presented the best clinical outcomes.

The Effect of Cumin cyminum L. Plus Lime Administration on Weight Loss and Metabolic Status in Overweight Subjects: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

BACKGROUND: Limited data are available regarding the effects of combined administration of Cumin cyminum L. and lime on weight loss and metabolic profiles among subjects with overweight subjects. OBJECTIVES: The current study aimed to assess the effects of combined administration of Cumin cyminum L. and lime on weight loss and metabolic profiles among subjects with overweight. PATIENTS AND METHODS: This randomized double-blind placebo-controlled clinical trial was conducted on 72 subjects with overweight, aged 18 - 50 years old. Participants were randomly divided into three groups: Group A received high-dose Cumin cyminum L. and lime capsules (75 mg each, n = 24), group B low-dose Cumin cyminum L. and lime capsules (25 mg each, n = 24) and group C placebos (n = 24) twice daily for eight weeks. RESULTS: After eight weeks of intervention, compared with low-dose C. cyminum L. plus lime and placebo, taking high-dose C. cyminum L. plus lime resulted in significant weight loss (in the high-dose group: -2.1 ± 1.7 vs. in the low-dose group: -1.2 ± 1.5 and in the placebo group: + 0.2 ± 1.3 kg, respectively; P < 0.001) and body mass index (-0.8 ± 0.6 vs. -0.5 ± 0.5 and +0.1 ± 0.5 kg/m2, respectively; P < 0.001). In addition, administration of high-dose C. cyminum L. plus lime compared with low-dose C. cyminum L. plus lime and placebo, led to a significant reduction in fasting plasma glucose (FPG) (P < 0.001) and a significant rise in quantitative insulin sensitivity check index (QUICKI) (+ 0.02 ± 0.02 vs. + 0.01 ± 0.02 and 0.01 ± 0.01, respectively; P = 0.01). Moreover, a significant decrease in serum triglycerides (-14.1 ± 56.2 vs. +13.9 ± 36.8 and + 10.6 ± 25.1 mg/dL; respectively; P = 0.03), total-cholesterol (-18.4 ± 28.6 vs. +8.6 ± 28.5 and -1.0 ± 24.8 mg/dL; respectively; P = 0.004) and low density lipoproteins- (LDL)-cholesterol levels (-11.8 ± 20.7 vs. +6.5 ± 23.2 and -2.9 ± 20.4 mg/dL, respectively; P = 0.01) was observed following the consumption of high-dose C. cyminum L. plus lime compared with low-dose C. cyminum L. plus lime and placebo. CONCLUSIONS: Results of the current study indicated that taking high-dose C. cyminum L. plus lime for eight weeks among subjects with overweight had beneficial effects on weight, BMI, FPG, QUICKI, triglycerides, total-cholesterol and LDL-cholesterol levels.