Antimicrobial Efficacy of Glass Ionomer Cement in Incorporation with Biogenic Zingiber officinale Capped Silver-Nanobiotic, Chlorhexidine Diacetate and Lyophilized Miswak

In the present study, Zingiber officinale is used for the synthesis of Zingiber officinale capped silver nanoparticles (ZOE-AgNPs) and compares the antimicrobial efficacy and compressive strength of conventional glass ionomer cement (GIC) combined with ZOE-AgNPs, lyophilized miswak, and chlorhexidine diacetate (CHX) against oral microbes. Five groups of the disc-shaped GIC specimens were prepared. Group A: lyophilized miswak and GIC combination, Group B: ZOE-AgNPs and GIC combinations, Group C: CHX and GIC combination, Group D: ZOE-AgNPs + CHX + GIC; Group E: Conventional GIC. Results confirmed the successful formation of ZOE-AgNPs that was monitored by UV-Vis sharp absorption spectra at 415 nm. The X-ray diffractometer (XRD) and transmission electron microscope (TEM) results revealed the formation of ZOE-AgNPs with a mean size 10.5–14.12 nm. The peaks of the Fourier transform infrared spectroscopy (FTIR) were appearing the involvement of ZOE components onto the surface of ZOE-AgNPs which played as bioreducing, and stabilizing agents. At a 24-h, one-week and three-week intervals, Group D showed the significantly highest mean inhibitory zones compared to Group A, Group B, and Group C. At microbe-level comparison, Streptococcus mutans and Staphylococcus aureus were inhibited significantly by all the specimens tested except group E when compared to Candida albicans. Group D specimens showed slightly higher (45.8 ± 5.4) mean compressive strength in comparison with other groups. The combination of GIC with ZOE-AgNPs and chlorhexidine together enhanced its antimicrobial efficacy and compressive strength compared to GIC with ZOE-AgNPs or lyophilized miswak or chlorhexidine combination alone. The present study revealed that The combination of GIC with active components of ZOE-AgNPs and chlorhexidine paves the way to lead its effective nano-dental materials applications.

Anti-PD-1 combined sorafenib versus anti-PD-1 alone in the treatment of advanced hepatocellular cell carcinoma: a propensity score-matching study

Background Vascular endothelial growth factor (VEGF) plays a role in the tumor microenvironment. Sorafenib, which inhibits the VEGF pathway, has an immune-modulation function but lacks substantial clinical data. This study aims to explore the efficacy of anti-PD-1 combined sorafenib in advanced hepatocellular carcinoma (HCC). Methods HCC patients who underwent anti-PD-1 treatment at Taipei Veterans General Hospital (Taipei, Taiwan) between January 2016 and February 2019 were reviewed. The efficacy was compared between groups after propensity-score matching. Results There were 173 HCC patients receiving anti-PD-1. After excluding unsuitable cases, 140 patients were analyzed, of which 58 received combination therapy and 82 received anti-PD-1 alone. The combination therapy had a trend of higher CR rate (8.6% vs. 4.9%, ns.), ORR (22.4% vs. 19.5%, ns.) and significantly higher DCR (69.0% vs. 37.8%, p < 0.05) comparing to anti-PD-1 alone. After matching, combination group achieved longer progression-free survival (3.87 vs. 2.43 months, p < 0.05) and overall survival (not reached vs. 7.17 months, p < 0.05) than anti-PD-1 alone, without higher grade 3/4 AE (10.3% vs. 7.1%, p = 0.73). The tumor response varied among different metastatic sites, with high responses in adrenal glands, peritoneum and lungs. The more AFP declined (> 10, > 50 and > 66%), the higher the ORR (70, 80 and 92%) and CR rates (30, 35 and 58%) were achieved at day 28. Conclusions This is the first study to demonstrate the combination of anti-PD-1 and sorafenib had better efficacy and survival benefit. A prospective randomized study is needed to confirm this finding.

Effectiveness of a Hydrophilic Curcumin-Based Formulation in Coadjuvating the Therapeutic Effect of Intravitreal Dexamethasone in Subjects With Diabetic Macular Edema

Purpose: This study evaluates if the addition of a curcumin formulation with a polyvinylpyrrolidone-hydrophilic carrier (CHC; Diabec®, Alfa Intes, Italy) to intravitreal injections of dexamethasone (DEX-IVT) can affect the morphological retinal characteristics, extending the steroid re-treatment period in patients with diabetic macular edema (DME).Methods: A randomized controlled clinical trial was carried out in DME patients, randomly assigned to receive DEX-IVT or DEX-IVT and a CHC. The evaluation of the mean difference of central retinal thickness (CRT) was the primary aim. Secondary aims were the evaluations of best-corrected visual acuity, differences in the predetermined retinal layer thickness, the number/time of re-treatment, and the assessment of safety.Results: A total of 73 DME patients were included (35 in the control group and 38 in the combined therapy group). In both the control and combined therapy groups, the mean CRT change from T0 to the 6 months’ evaluation was significant (p = 0.00). The mean CRT result was significantly different at month 4 (p = 0.01) between the control and combined therapy groups, with a greater reduction in the combined therapy group, in particular, in patients with ≤10 years of diabetes. A trend of CRT reduction in the combined therapy group has been observed also considering patients with subfoveal neuroretinal detachment. In addition, we observed that the reduction of inner retinal layer thickness was greater in the combination group, in comparison with controls.Conclusion: The combination of a CHC to DEX-IVT is a promising therapeutic option in case of DME, in particular, for patients with early-stage diabetes and with an inflammatory phenotype. Further studies will be necessary to confirm these findings.

The effect of combination probiotic lactobacillus brevis and leuconostoc mesenteroides on tgf-β and il-12 expression in ileum

Background: Asthma is a disease of the respiratory tract in the form of chronic inflammation. Chronic inflammation is one of them characterized by the remodeling of the airways mediated by the anti-inflammatory cytokine TGF-β. In addition there are also several immune cells that play a role such as macrophages, dendritic, neutrophils as producers of IL-12. The presence of the gut-lung axis allows the spread of inflammatory cytokines from the lungs to the intestines and vice versa. Lactobacillus brevis and Leuconostoc mesenteroides have the potential to modulate the immune system through its colonization of the gut. The study aimed to look at the effect of probiotics combined Lactobacillus brevis and Leuconostoc mesenteroides on the expression of TGF-β and IL-12 in the asthma model mouse ileum. Method: This experimental post-test only control group design study used 18 Sprague-Dawley mice. The mice were divided into 3 groups at random: control group (KI), asthma treatment (KII), asthma treatment with a combination of Lactobacillus brevis and Leuconostoc mesenteroides (KIII). Sensitization of asthma with OVA through intraperitoneal injection on days 0 and 14 and through inhalation on days 21 -63. Administration of combination probiotics per oral per day on days 21-63 after inhalation of OVA. The ileum network was taken on the 64th day and measured the expression of TGF-βand IL-12 with immunohistochemical methods and analyzed the percentage proportion of TGF-βand IL-12. Data analysis were conducted by One way ANOVA test and continued post hoc tests. Results: The percentage calculation of the proportion of TGF-βin thecontrol group (KI), asthma group (KII), and the combination group of L.brevis and L.mesenteroides (KIII) is 22.4 ± 15.27; 1.6 ± 2.12; 19.4 ± 6.65. While the percentage calculation of il-12 proportion in each group consecutively were 24.3 ± 19.67; 64.63 ± 9.90; 51 ± 16.62. One way ANOVA Test results on the percentage proportion of TGF-βhave a p value of 0.013 (p<0.05) which means there is a significant difference in the entire group. Furthermore, the Post Hoc Games-Howell test was conducted and obtained a p value of 0.003 (p<0.05) between the asthma group (KII) and the combination group of L.brevis and L.mesenteroides (KIII) which means there are significant differences between the two groups. One way ANOVA Test results on the percentage proportion of IL-12 have a p value of 0.011 (p<0.05) which means there is a significant difference in the entire group. Furthermore, the Post Hoc LSD test was conducted and obtained a p value of 0.001 (p<0.05) between the control group Post Hoc analyses was conducted and obtained a p value of 0.002 (p<0.05) with number of errors was 11.353 between the control group (KI) and asthma group (KII) which means there are significant differences between the two groups. Conclusion: The probiotic administration of lactobacillus brevis and Leuconostoc mesenteroides had no effect on the expression of TGF-β and had no effect on il-12 expression in the asthma model mouse ileum. It is necessary to do research on mice with asthma using combinations with other bacteria in order to get maximum effect. Bangladesh Journal of Medical Science Vol. 21(1) 2022 Page : 175-183

Vitamin D Status in Prediabetes and its Different Categories

Objectives: Data regarding vitamin D level and status among categories of prediabetes are scarce in the literature. This study is aimed to determine the level and status of vitamin D among adults with prediabetes and its different categories. Materials and methods: This crosssectional study was carried out in 111 newly detected adults with prediabetes according to American Diabetes Association 2018 criteria and 74 matched healthy control (normal glucose tolerance). People with prediabetes were categorized into impaired glucose tolerance, impaired fasting glucose and their combination group. Participants were recruited consecutively from the Department of Endocrinology, BSMMU to measure serum 25 hydroxyvitamin D by high performance liquid chromatography and serum intact parathormone, calcium, albumin and phosphate by chemiluminescent enzyme-labeled immunometric assay. Results: Vitamin D level and status were not significantly different between people with prediabetes & control and also in different categories of prediabetes. Severe vitamin D deficiency was significantly higher in people with prediabetes (27.5% vs 10%, p= 0.05). There were no associations between different blood glucose levels with vitamin D among adults with prediabetes. Conclusions:Vitamin D was not associated with prediabetes or its categories. Bangladesh Journal of Medical Science Vol. 21(1) 2022 Page : 120-128

In vitro analysis of synergistic effect of honey against chemically induced hepatic insult in Balb/c mice.

Human being knows honey since thousands of years for its nutritional and medicinal values. Traditional medicine systems like Ayurveda have elaborated honey as boon for health and patient care. Synergistic effect of honey was research but to a limited extend. Honey is advised with Picrorhiza kurroa for hepatic disorders or hepato-protection in Ayurveda. Here we have examined in vitro synergistic effect of honey when given with Picrorhiza kurroa in acetaminophen-induced hepatotoxicity in Balb/c mice model. We obtained Serum and liver lysate to check levels of hepatic markers, Alkaline phosphatase and Glutathione. The level of alkaline phosphatase raised while glutathione level is reduced during hepatic offence. We observed a compensation of above markers when P. Kurrua, honey and its combination were used in acetaminophen induced hepatic toxicity. We observed a better mice weight gain in combination group (Group IV) compared to control group. This study can pave a way for future research on honey as a better adjuvant for hepatotoxic drugs and other herb-drug interactions researches.

Neural Function Recovery and Safety of Mild Hypothermia Therapy Combined with Monosialotetrahexosylganglioside on Neonatal Asphyxia Complicated by Hypoxic Ischemic Encephalopathy

Objective. To explore the effect and safety of mild hypothermia therapy combined with monosialotetrahexosylganglioside (GM1) on neural function recovery of neonatal asphyxia complicated by hypoxic ischemic encephalopathy (HIE). Methods. The clinical data of 90 neonates with HIE were retrospectively analyzed. According to the treatment methods, the neonates were divided into a routine group, a mild hypothermia group, and a combination group, with 30 cases in each group. The differences in neural function recovery, biochemical indexes, clinical signs recovery, efficacy, and complications were observed in the three groups after treatment. Results. After treatment, the score of neonatal behavioral neurological assessment (NBNA) and level of superoxide dismutase (SOD) in the combination group were higher than those of the other two groups ( P < 0.05 ). The levels of neuron-specific enolase (NSE), S-100β protein, and plasma neuropeptide Y (NPY) in the combination group were lower than those in the other two groups, and the recovery time of consciousness, muscle tension, and reflex was shorter ( P < 0.05 ). The combination group showed higher total effective rate and lower incidence of complications as compared with the other two groups ( P < 0.05 ). Conclusion. Mild hypothermia therapy combined with GM1 for the treatment of neonatal asphyxia complicated by HIE can promote the recovery of neural function and reduce the incidence of complications in neonates.

Associations of Occupational Heat Stress and Noise Exposure with Carotid Atherosclerosis among Chinese Steelworkers: A Cross-Sectional Survey

Occupational exposure to heat stress and noise at the workplace are widespread physical hazards and have been associated with an increase in both morbidity and mortality. This study aims to examine the association between occupational heat stress and noise exposure and carotid atherosclerosis in Chinese steelworkers. A total of 3471 subjects were included in this study. Carotid plaque was measured using ultrasonography. The occupational information was collected by face-to-face personal interviews and all of the reported information was verified with the company’s records. Workers were divided into non-exposure and exposure groups according to the company’s records regarding previous and/or current heat stress and noise exposure status in the workplace. The prevalence of carotid plaque was 30.1% in the study population and workers exposed to both occupational heat stress and noise had the highest prevalence of carotid plaque at 37.2%. The odds of carotid plaque in individuals of different exposure status were significantly elevated after adjustment for potential confounders, especially in the heat stress and noise exposure combination group: OR = 1.32, 95% CI: 1.06 to 1.65, in individuals who had experienced heat stress exposure; OR = 1.49, 95% CI: 1.18 to 1.88, in individuals who had experienced noise exposure; OR = 2.02, 95% CI: 1.60 to 2.56, in the combination group. No significant association in female workers and no significant multiplicative or additive interactions were found between occupational heat stress and noise exposure and carotid plaque. Exposure to occupational heat stress and noise are statistically associated with carotid atherosclerosis among male steelworkers.

Deferasirox combination with eltrombopag shows anti-myelodysplastic syndrome effects by enhancing iron deprivation–related apoptosis

Iron overload (IO) affected the survival of patients with myelodysplastic syndrome (MDS). Deferasirox (DFX) is widely used in patients with MDS for iron chelation therapy, but is not suitable for MDS patients with severe thrombocytopenia. Eltrombopag (ELT) is a type of thrombopoietin receptor (TPOR) analog used in the treatment of thrombocytopenia. Therefore, we sought to explore the synergistic effects and possible mechanisms of DFX combination with ELT in MDS cells. In our study, the combination of DFX with ELT synergistically inhibited proliferation, induced apoptosis and arrested cell cycle of MDS cells. Through the RNA-sequence and gene set enrichment analysis (GSEA), iron metabolism–related pathway played important roles in apoptosis of SKM-1 cells treated with DFX plus ELT. Transferrin receptor (TFRC) was significantly highly expressed in combination group than that in single agent groups, without affecting TPOR. Furthermore, the apoptosis of the combination group MDS cells could be partially reversed by ferric ammonium citrate (FAC), accompanied with decreased expression of TFRC. These results suggested that the combination of DFX and ELT synergistically induced apoptosis of MDS cells by enhancing iron deprivation–related pathway.

Low dose dexamethasone in combination with Remdesivir does not cause immune dysregulation

BackgroundThe administration of Remdesivir/Dexamethasone combination on T and B cell responses in patients with COVID-19 is sparse. To compare cell mediated immune response in patients treated with only Remdesivir and Remdesivir/dexamethasone combinationStudy DesignProspective, cohort studyMethodsRT-PCR positive SARS-CoV-2 patients (n=49) were enrolled. Patients not requiring O2-supplementation were on remdesivir and those requiring were on remdesivir/dexamethasone. Baseline parameters (complete blood picture, inflammatory markers), T and B cells (flow cytometry: day 5 and 30) and neutralizing antibodies (chemiluminescence: day 30) were estimated. Students “t’’ test was used to evaluate the differences.ResultsOf the 49 patients, 26 (Mean age-44.68±13.45) were treated with remdesivir and 23 (Mean age-48.33±14.76) with remdesivir/dexamethasone combination. While blood counts and immune cells increased, inflammatory markers decreased post treatment in both the groups. A significant increase in WBC (6357±981Vs10700±1363; p=0.01), absolute neutrophil counts (4578±711Vs8256±1323; p=0.01) with decrease in levels of CRP (31±7.1Vs10±4.2; p=0.01), D-Dimer (172.3±8Vs118.1±12; p=0.0005), IL6 (17.6±3.8Vs1.72±0.2; p=0.0001), CD4 cells (2681±86Vs1256±369; p=0.0003), CD8 cells (1749±88 Vs 1256±221; p=0.01) and neutralizing antibodies were seen post treatment in the combination group. Correction of hypoxia and maintenance of oxygen >95% was also noted. ConclusionRemdesivir/dexamethasone combination given to patients requiring oxygen supplementation is safe at 4-6mg/day and showed a marked decrease in inflammation and no immune dysregulation.