Fetal neural stem cells from a mouse model of 15q11-13 duplication syndrome exhibit altered differentiation into neurons and astrocytes

The duplication of human chromosome 15q11-13 is known to be associated with an estimated 1.1% of autism cases. Here, we investigated whether differentiation into neurons and astrocytes is altered in fetal neural stem cells (FNSCs) isolated from the mouse model of 15q11-13 duplication syndrome (patDp/+ mice). In patDp/+ mice-derived FNSCs, multipotency was maintained for a longer period, the population of neurons was downregulated, and that of astrocytes was upregulated significantly after differentiation induction. These results suggest that the dysregulation of FNSCs differentiation could affect cortical development and behavioral deficits in the early postnatal stage shown in the patDp/+ mice.     

Immunolocalization of murine type VI 3β-hydroxysteroid dehydrogenase in the adrenal gland,testis, skin,and placenta

The enzyme 3β-hydroxysteroid dehydrogenase/isomerase (3β-HSD) is essential for the biosynthesis of all active steroid hormones, such as those secreted from the adrenal gland, testis, ovary, skin and placenta. The 3β-HSD enzymes exist in multiple isoforms in humans and rodents. To date, six different isoforms have been identified in the mouse, and these isoforms are speculated to play different roles in different tissues. We previously showed that the murine type VI 3β-HSD isoform (Hsd3b6) is expressed specifically in the aldosterone-producing zona glomerulosa cells within the adrenal gland and that its overexpression causes abnormally increased aldosterone synthesis, revealing a crucial (or rate-limiting) role of this enzyme in steroidogenesis. However, potential contributions of this enzyme to the steroid hormone synthesis outside the adrenal glands are poorly understood. This paucity of knowledge is partly because of the lack of isoform-specific antibody that can be used for immunohistochemistry. Here, we report the development and characterization of specific antibody to Hsd3b6 and show the results of immunohistochemistry for the adrenal gland, testis, ovary, skin and placenta. As expected, Hsd3b6 immunoreactivities within the adrenal gland were essentially confined to the zona glomerulosa cells, where aldosterone is produced. By contrast, no immunopositive cells were observed in the zona fasciculata, which is where corticosterone is produced. In the gonads, while the ovaries did not show any detectable immunoreactivity to Hsd3b6, the testes displayed intense immunoreactivities within the interstitial Leydig cells, where testosterone is produced. In the skin, positive immunoreactivities to Hsd3b6 were only seen in the sebaceous glands, suggesting a specific role of this enzyme in sebaceous function. Moreover, in the placenta, Hsd3b6 was specifically found in the giant trophoblast cells surrounding the embryonic cavity, which suggests a role for this enzyme in local progesterone production that is required for proper embryonic implantation and/or maintenance of pregnancy. Taken together, our data revealed that Hsd3b6 is localized in multiple specific tissues and cell types, perhaps thereby involved in biosynthesis of a number of tissue-specific steroid hormones with different physiological roles.     

Effects of exercise on C-reactive protein,inflammatory cytokine and adipokine in patients with type 2 diabetes: A meta-analysis of randomized controlled trials

Objective

C-reactive protein (CRP), inflammatory cytokines, and adipokines contribute to atherosclerosis, insulin resistance, and development of late-onset complication in patients with type 2 diabetes. We performed a systematic review to assess effects of exercise interventions on inflammatory markers/cytokines and adipokines.

Materials/Methods

We searched electronic databases (MEDLINE, EMBASE, and Cochrane Controlled Trials Registry) and reference lists in relevant papers for articles published in 1966–2013. We selected studies that evaluated the effects of exercise intervention on inflammatory markers/cytokines and adipokines in adult patients with type 2 diabetes. Weighted mean differences of exercise on outcomes were derived using fixed or random effect models; factors influencing heterogeneity were identified using meta-regression analysis.

Results

Fourteen randomized controlled trials (824 patients) were included in our meta-analysis. Exercise was associated with a significant in CRP = − 0.66 mg/l (95% CI, − 1.09 to − 0.23 mg/l; − 14% from baseline) and interleukin-6 (IL-6) = − 0.88 pg/ml (95% CI, − 1.44 to − 0.32 pg/ml; − 18% from baseline) but did not alter adiponectin or resistin levels; aerobic exercise program was associated with a significant change in leptin = − 3.72 ng/ml (95% CI, − 6.26 to − 1.18 ng/ml; − 24% from baseline). For IL-6, exercise was more effective in those with a longer duration in the program and larger number of sessions during study (p = 0.001).

Conclusions

Exercise decreases inflammatory cytokine (CRP and IL-6) in patients with type 2 diabetes. Exercise could be a therapeutic option for improving abnormalities in inflammation levels in patients with diabetes.     

High levels of anti-SSA/Ro antibodies in COVID-19 patients with severe respiratory failure: a case-based review

Clinical Rheumatology - We treated two patients with severe respiratory failure due to coronavirus disease 2019 (COVID-19). Case 1 was a 73-year-old woman, and Case 2 was a 65-year-old-man. Neither...     

Mediastinal Malignant Melanoma Markedly Shrinking in Response to Nivolumab

Primary malignant melanoma (MM) of the mediastinum is rare, and there is a lack of consensus regarding the preferred treatment because non-cutaneous MM demonstrates an inferior response to systemic therapy. Herein, we describe the case of a 73-year-old man with MM of the anterior mediastinum with multiple liver metastases. Even though the size of lesions increased rapidly following diagnosis, nivolumab monotherapy caused remarkable tumor shrinkage. This is the first report of mediastinal MM showing a significant response to nivolumab. We, therefore, suggest that immunotherapy may be one of the treatment options for primary mediastinal MM.     

Recent progress in the use of diaziridine-based sweetener derivatives to elucidate the chemoreception mechanism of the sweet taste receptor

All sweeteners are recognized by the sweet taste receptor (T1R2–T1R3). The elucidation of the chemoreception mechanism of receptor–ligand interactions is an attractive topic for researchers. Molecular biology and computational biology techniques can reveal the proposed mechanisms for this topic. Other approaches, including chemical biology (bioorganic chemistry), have helped to identify mechanisms on the basis of molecular structure. In this mini-review, we have summarized the recent progress in the synthesis of sweetener derivatives, which includes the use of photoaffinity labeling of diazirine-based derivatives to elucidate the chemoreception of sweeteners.

The review summarized recent progress for the elucidation of the chemoreception mechanism of sweet taste receptor–sweetener interactions with photoaffinity labeling.