Efficacy of teplizumab for treatment of type 1 diabetes: A meta-analysis of randomized controlled trials.

BACKGROUND: The management of Type 1 Diabetes Mellitus (T1DM) is a significant clinical challenge. This study evaluated the efficacy of teplizumab, an immunomodulatory drug, in patients with T1DM, using a systematic review and meta-analysis approach. METHODS: We systematically searched multiple databases including Medline, Scopus, and others up to 10 January 2024, without language or regional restrictions. We included randomized controlled trials (RCTs) comparing teplizumab with placebo in T1DM patients. RESULTS: Our analysis incorporated 8 RCTs, predominantly involving participants aged 7-35 years, diagnosed with T1DM and treated with 14-day courses of teplizumab. The primary outcomes included insulin use, C-peptide levels, and HbA1c levels. We observed a significant reduction in insulin use in the teplizumab group standardised mean difference of -0.50 (95% Confidence Interval [CI]: -0.76 to -0.23, p < 0.001; I2 = 49%). C-peptide levels were consistently higher in the teplizumab group, indicating improved endogenous insulin production. However, no significant change was noted in HbA1c levels between the groups. Quality assessment indicated a low risk of bias in most studies. CONCLUSIONS: Teplizumab has a significant impact on reducing insulin dependence and enhancing endogenous insulin production in T1DM patients. However, its effect on long-term glycaemic control, as indicated by HbA1c levels, remains inconclusive.

Incident diabetes in adolescents using antidepressant: a systematic review and meta-analysis.

BACKGROUND: The use of antidepressants has been on the rise among adolescents and young adults, populations also increasingly at risk for type 2 diabetes. However, the relationship between antidepressant uses and diabetes incidence in these age groups remains poorly understood. METHODS: Adhering to PRISMA guidelines and the Cochrane Handbook, we conducted a comprehensive search in PubMed, Scopus, Embase, and Web of Science up to 21 February 2024, registering our protocol on PROSPERO (CRD42024516272). RESULTS: Six studies, ranging from 16, 470 to 1, 582, 914 participants and spanning 2010 to 2023 across North America, Europe, and Asia, were included. The meta-analysis revealed a significant association between antidepressant use and diabetes onset, with 10 cases per 1, 000 observations (p < 0.01; I2 = 100%). Adolescents using high doses of antidepressants showed a 62% increased risk of developing diabetes compared to non-users or those on low doses (Risk ratio = 1.67; 95% CI 1.19-2.35; I2 = 87%; p < 0.01). The overall quality of the studies was high, with an average Newcastle-Ottawa Scale score of 7.66. Sensitivity analysis highlighted the robustness of these findings, except when removing specific studies, indicating potential sources of heterogeneity. CONCLUSION: Antidepressant use in adolescents is associated with a significantly increased risk of diabetes onset, particularly at higher doses. This finding underscores the necessity for vigilant monitoring of glucose levels in this population and warrants further investigation into the underlying mechanisms and long-term outcomes.

Constructing a novel competing Endogenous RNAs network based on NR3C1 and X-linked inhibitor of apoptosis protein genes reveals potential prognostic biomarkers in colorectal cancer.

Background: Long noncoding RNAs (lncRNAs) have been recognized as the main modulatory molecules in various cancers and perform as competing endogenous RNAs (ceRNAs). The nuclear hormone receptor superfamily of ligand-activated transcription factors (NR3C1) regulates numerous proliferative and metabolic processes such as tumorigenesis and metabolic diseases. Furthermore, X-linked inhibitor of apoptosis protein (XIAP) belongs to a family of the inhibitors of apoptosis proteins, is located downstream of the glucocorticoid receptor (GR or NR3C1) pathway, and cooperates with GR to suppress apoptosis. However, the underlying mechanisms of NR3C1 and XIAP in colorectal cancer (CRC) remain mainly unclear. This research aims to clarify the potential RNA biomarkers and to construct a novel ceRNA network in CRC. Materials and Methods: Multistep bioinformatics methods such as Lnc2cancer and miRDB databases were applied to identify candidate lncRNAs and miRNAs. The interaction energy between lncRNAs, NR3C1, and XIAP genes was analyzed by the LncRRIsearch database. Plus, microRNAs and lncRNA were evaluated via the Diana tools database to select microRNAs with the most binding scores. Quantitative reverse transcription-polymerase chain reaction (QRT-PCR) was applied to verify RNA molecules' expression levels and their association with the clinicopathological factors in 30 CRC tissues compared to 30 adjacent tissues. Results: QRT-PCR showed upregulation of KCNQ1OT1, NR3C1, and XIAP and downregulation of miR-421. The ceRNA network was constructed with 17 lncRNAs, 2 mRNAs, and 42 miRNAs. Thus, we explained the potential interactions between KCNQ1OT1 and miR-421 with NR3C1 and XIAP genes. Conclusion: Our study represents potential prognostic biomarkers and a new ceRNA network for further study in CRC.

Emerging pharmacotherapy for the treatment of cannabis use disorder.

INTRODUCTION: About one-fifth of cannabis users, the most commonly used illicit substance, have cannabis use disorder (CUD). Psychiatric disorders and suicide are more common in these patients, and the disability-adjusted life years were reported to be 0.69 million. Pharmacotherapy for CUD is an unmet public health need, as current evidence-based therapies have limited efficacy. AREAS COVERED: After explaining the pathophysiology of CUD, the effects of emerging pharmacological interventions in its treatment obtained from randomized controlled trials were reviewed in light of mechanisms of action. Superiority over control of cannabidiol, gabapentin, galantamine, nabilone plus zolpidem, nabiximols, naltrexone, PF-04457845, quetiapine, varenicline, and topiramate were observed through the cannabinoid, glutamatergic, γ-aminobutyric acidergic, serotonergic, noradrenergic, dopaminergic, opioidergic, and cholinergic systems. All medications were reported to be safe and tolerable. EXPERT OPINION: Adding pharmacotherapy to psychotherapy is the optimal treatment for CUD on a case-by-case basis. Drug development to add to psychotherapy is the main path, but time and cost suggest repurposing and repositioning existing drugs. Considering sample size, follow-up, and effect size, further studies using objective tools are necessary. The future of CUD treatment is promising.

Statin therapy improves outcomes in infective endocarditis: evidence from a meta-analysis.

BACKGROUND: Beyond its ability to decrease cholesterol, statin medication has been proved to have a variety of pleiotropic effects, such as anti-inflammatory and immunomodulatory effects. Statins are an appealing therapeutic option for individuals with infective endocarditis because of these effects, as the condition is linked to a strong inflammatory response. METHODS: A comprehensive search was done in Medline/PubMed, Cochrane database (CENTRAL), and Google Scholar to identify relevant studies reporting outcomes of interest (rate of mortality, intensive care unit admission, and embolic events) comparing those who are on statin therapy to nonusers were included. We performed a random effect meta-analysis to pool each study's individual results. RESULTS: Three articles were included in the study. The pooled results regarding our primary endpoint showed there was a significant reduction in mortality among statin users in all time points (1-year mortality: OR 0.69, 95% CI 0.61-0.79, I2: 0%; Chi2 = 0.01; p < 0.0001). Meta-analysis for the secondary outcome showed statin users are less frequently admitted to the intensive care unit (OR 0.73, 95% CI 0.59-0.90, I2: 0%; Chi2 = 0.00; p = 0.0004). The rate of mortality was significantly lower for those with a previous history of cerebrovascular disease who were on statin therapy compared to those without cerebrovascular diseases (CVD). CONCLUSIONS: The results of the present study support a significant association with statin therapy as a potential treatment proposed for individuals at risk of infective endocarditis.

A survey on causes of amputation in a 9-year period in Iran.

BACKGROUND: Limb loss occurs as a result of different causes and has been increasing in many countries. This study determines the demography of amputees in one of the relatively large cities of Iran. METHODS: This retrospective study was undertaken on all of the amputees between 2003 and 2011. Patients' demographics including age, sex, the limb that had undergone amputation, etiology of limb loss and side and level of amputation were recorded. Also, the level of amputation was recorded as minor (below wrist or ankle) or major (above wrist or ankle). RESULTS: In total, 624 patients were enrolled in the study. The number of amputees was from 53 to 118/year. Of the patients, 508 were male (81.4 %) and 118 were female (18.6 %). The men with amputation were younger on average than women; 61.9 % of the amputations (386) were major and 38.1 % were minor (238). Overall, the most common cause of amputation was trauma and the most common level was transmetatarsal. The most common level for major amputations was below knee. CONCLUSION: In contrast to similar studies in developed countries, trauma was found to be the major cause of all types of amputations and in all age groups, which emphasizes the need for preventive measures in the country.

Malachite Green, the hazardous materials that can bind to Apo-transferrin and change the iron transfer.

Different groups of synthetic dyes might lead to environmental pollution. The binding affinity among hazardous materials with biomolecules necessitates a detailed understanding of their binding properties. Malachite Green might induce a change in the iron transfer by Apo-transferrin. Spectroscopic studies showed malachite green oxalate (MGO) could form the apo-transferrin-MGO complex and change the Accessible Surface Area (ASA) of the key amino acids for iron transfer. According to the ASA results the accessible surface area of Tyrosine, Aspartate, and Histidine of apo-transferrin significantly were changed, which can be considered as a convincing reason for changing the iron transfer. Moreover, based on the fluorescence data MGO could quench the fluorescence intensity of apo-transferrin in a static quenching mechanism. The experimental and Molecular Dynamic simulation results represented that the binding process led to micro environmental changes, around tryptophan residues and altered the tertiary structure of apo-transferrin. The Circular Dichroism (CD) spectra result represented a decrease in the amount of the α-Helix, as well as, increase in the ß-sheet volumes of the apo-transferrin structure. Moreover, FTIR spectroscopy results showed a hypochromic shift in the peaks of amide I and II. Molecular docking and MD simulation confirmed all the computational findings.

Molecular aspects of the interaction of spermidine and α-chymotrypsin.

Polyamines such as spermidine are essential for survival. The purpose of the present study was to investigate how spermidine could influence the conformation, thermal stability and the activity of α-chymotrypsin. The influence of spermidine on the structure and stability of α-Chymotrypsin (α-Chy) explored using different spectroscopy method and molecular docking simulations. The stability and activity of α-Chy were increased in the presence of spermidine. Increasing of the α-Chy absorption in the presence of spermidine was as a result of the formation of a spermidine - α-Chy complex. The results of fluorescence spectroscopic measurements suggested that spermidine has a vigorous ability to quench the intrinsic fluorescence of α-Chy through the dynamic quenching procedure. Near and Far-UV CD studies also confirmed the transfer of aromatic residues to a more flexible environment. The absorption increasing of α-Chy in the presence of spermidine was as a result of the formation of spermidine - α-Chy complex. Molecular docking results also revealed the presence of one binding site with a negative value for the Gibbs free energy of the binding of spermidine to α-Chy. Further, the docking study revealed that van der Waals interactions and hydrogen bonds play a main role in stabilizing the complex.