Silver carbene complexes: An emerging class of anticancer agents

Cancer is a major global health problem with large therapeutic challenges. Although substantial progress has been made in cancer therapy, there still remains a need to develop novel and effective treatment strategies to treat several relapsed and refractory cancers. Recently, there has been growing demand for considering organometallics as antineoplastic agents. This review is focused on a group of organometallics, silver N-heterocyclic carbene complexes (SCCs) and their anticancer efficacy in targeting multiple pathways in various in vitro cancer model systems. However, the precise molecular mechanism of SCCs anticancer properties remains unclear. Here, we discuss the SCCs chemistry, potential molecular targets, possible molecular mechanism of action, and their application in cancer therapies.     

Microbiome‐immune‐metabolic axis in the epidemic of childhood obesity: Evidence and opportunities

Obesity epidemic responsible for increase in diabetes, heart diseases, infections and cancer shows no signs of abating. Obesity in children is also on rise, indicating the urgent need of strategies for prevention and intervention that must begin in early life. While originally posited that obesity results from the simple concept of consuming more calories, or genetics, emerging research suggests that the bacteria living in our gut (gut microbiome) and its interactions with immune cells and metabolic organs including adipose tissues (microbiome‐immune‐metabolic axis) play significant role in obesity development in childhood. Specifically, abnormal changes (dysbiosis) in the gut microbiome, stimulation of inflammatory cytokines, and shifts in the metabolic functions of brown adipose tissue and the browning of white adipose tissue are associated with increased obesity. Many factors from as early as gestation appear to contribute in obesity, such as maternal health, diet, antibiotic use by mother and/or child, and birth and feeding methods. Herein, using evidence from animal and human studies, we discuss how these factors impact microbiome‐immune‐metabolic axis and cause obesity epidemic in children, and describe the gaps in knowledge that are warranted for future research.     

Oxidative stress and antioxidant capacity in patients with chronic pancreatitis with and without diabetes mellitus

Aim

To determine oxidant stress and antioxidant capacity in chronic pancreatitis (CP) patients with and without diabetes mellitus.

Methods

This study is a secondary data analysis of our earlier study on 127 (male?=?86) patients with CP, grouped as those with diabetes (case; n?=?23) and those without diabetes (control). Markers of antioxidant status included vitamins A and E, total antioxidant capacity (TAC; measured as ferric-reducing ability of plasma [FRAP]), and total glutathione (T-GSH). Markers for oxidative stress included lipid peroxidation, measured as thiobarbituric acid reactive substances (TBARS) and serum superoxide dismutase (s-SOD).

Results

Patients with diabetes were older (mean [SD] age 36.4 [9.7] vs. 29.3 [10.0] years; p?=?0.032), had longer duration of CP [4 (0.3?C21) vs. 3 (0.3?C24) years; p?=?0.07), and had a lower TAC (269.8 [92.4] vs. 355.5 [128.6] ??moles Fe⁺² liberated; p?=?0.003) compared to those without diabetes. In multiple logistic regression analysis taking all exploratory variables, FRAP (<270 ??moles Fe⁺² liberated) was associated with diabetes independent of duration of CP, age of patients, and TBARS levels. However, oxidative stress levels were not different between diabetic and nondiabetic patients.

Conclusions

Diabetes was found to be associated with longer duration of CP and with low antioxidant capacity. Further studies will be needed to evaluate a causal association.     

Ambient Light Regulates Retinal Dopamine Signaling and Myopia Susceptibility

PurposeExposure to high-intensity or outdoor lighting has been shown to decrease the severity of myopia in both human epidemiological studies and animal models. Currently, it is not fully understood how light interacts with visual signaling to impact myopia. Previous work performed in the mouse retina has demonstrated that functional rod photoreceptors are needed to develop experimentally-induced myopia, alluding to an essential role for rod signaling in refractive development.MethodsTo determine whether dim rod-dominated illuminance levels influence myopia susceptibility, we housed male C57BL/6J mice under 12:12 light/dark cycles with scotopic (1.6 × 10⁻³ candela/m²), mesopic (1.6 × 10¹ cd/m²), or photopic (4.7 × 10³ cd/m²) lighting from post-natal day 23 (P23) to P38. Half the mice received monocular exposure to −10 diopter (D) lens defocus from P28–38. Molecular assays to measure expression and content of DA-related genes and protein were conducted to determine how illuminance and lens defocus alter dopamine (DA) synthesis, storage, uptake, and degradation and affect myopia susceptibility in mice.ResultsWe found that mice exposed to either scotopic or photopic lighting developed significantly less severe myopic refractive shifts (lens treated eye minus contralateral eye; –1.62 ± 0.37D and −1.74 ± 0.44D, respectively) than mice exposed to mesopic lighting (–3.61 ± 0.50D; P < 0.005). The 3,4-dihydroxyphenylacetic acid /DA ratio, indicating DA activity, was highest under photopic light regardless of lens defocus treatment (controls: 0.09 ± 0.011 pg/mg, lens defocus: 0.08 ± 0.008 pg/mg).ConclusionsLens defocus interacted with ambient conditions to differentially alter myopia susceptibility and DA-related genes and proteins. Collectively, these results show that scotopic and photopic lighting protect against lens-induced myopia, potentially indicating that a broad range of light levels are important in refractive development.