Genistein suppresses microglial activation and inhibits apoptosis in different brain regions of hypoxia-exposed mice model of amnesia.

Genistein (GE) or 4',5,7-trihydroxyflavone, a plant derived isoflavone, is a biologically active compound having several beneficial properties. Studies showed that GE possesses anti-neoplastic, anti-tumor, anti-helminthic, anti-oxidant, and anti-inflammatory activities. Herein, we investigated the neuroprotective effects of GE in a mouse model of hypoxia-induced amnesia. Mice were exposed to hypoxic conditions (10% O2) in a designated hypoxia chamber and co-treated with GE (10, 20, or 30 mg/kg) for 4 weeks. Following this, behavioral tests were performed to evaluate memory performance. We assessed microglial activation in the hippocampus, amygdala, and pre-frontal cortex (PFC) regions by evaluating the Iba-1 and GFAP transcript levels, and MIP-1ß, Cox-2, and IL6 protein levels. Apoptosis was assessed by evaluating Bax, BAD, and Bcl-2 mRNA levels, and caspase-3 activity. To uncover the underlying molecular mechanism, we evaluated the levels of Nrf2, HO-1, and NQO1 in different brain regions of mice from all groups. Results showed that hypoxia-exposed mice have reduced performance in the behavioral tests and GE treatment enhanced the memory performance in hypoxia-exposed mice. Moreover, hypoxia-exposed mice showed increased expression of microglial activation markers and enhanced apoptosis in the hippocampus, amygdala, and PFC. GE treatment suppressed microglial activation and prevented apoptosis in the brain of hypoxia-exposed mice. Furthermore, hypoxia-exposure reduced the expression of Nrf2, NQO1, and HO-1 while GE treatment ameliorated this decrease in different regions of hypoxia-exposed mice brain. In conclusion, GE prevents cognitive dysfunction by suppressing microglial activation and inhibiting apoptosis in the hypoxia-exposed mice brain.

The Potential Efficacy of ß-Blockers on Melanoma Survival: A Narrative Review.

Melanoma is a common tumor accounting for around 3–5% of all cutaneous malignancies with worldwide increasing incidence. It is still associated with significant mortality despite the breakthrough of new innovative therapies within the last decade. A wide variety of treatment modalities is currently used for the management of melanoma, ranging from surgical excision of primary melanoma to adju-vant and palliative treatment with target molecules, including BRAF and MEK inhibitors, and immune checkpoint inhibitors. β-blockers have recently demonstrated in preclinical and clinical studies to reduce recurrence and to correlate with better overall survival in meta-static melanoma as an additional supportive treatment option, owing to their anti-tumor potential. Further investigation regarding their efficacy and safety profile is needed, since there are only few studies in the literature on this topic. Our aim is to evaluate the role and current status of β-blockers in melanoma management. The literature research includes peer-reviewed articles (clinical trials or scien-tific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) till May 2020 and reference lists of respective articles. Only articles published in English language were included. J Drugs Dermatol. 20(4):380-383. doi:10.36849/JDD.5673.

Home remedies in different pediatric dermatoses: An observational study.

Traditional medicinal systems are widely practiced in the Indian subcontinent for a wide variety of diseases. We aimed to identify the various home remedies used by people to treat numerous pediatric dermatoses. It was an observational study carried out over 18 months in which 150 children attending our clinics were recruited. A detailed history regarding the various indigenous preparations used was taken from caregivers and noted in a proforma. A total of 150 children (M:F-89:61) aged between 4 months to 18 years were included. Atopic dermatitis and eczema (n = 28) were the most common dermatoses whereas the most common home remedies used for these either solo or in combination were coconut oil (13), olive oil (11), mustard oil (7), aloevera gel (6), ghee (6), curd (4), and honey (2). Acne was the second most common dermatoses (n = 22), products used for acne were Fuller's earth, aloevera gel, turmeric, gram flour, mustard oil, lime and sandalwood paste. Other dermatoses treated by indigenous products included impetigo and other bacterial infections, seborrheic dermatitis, dermatophytoses, verruca, molluscum, hypopigmentary disorders, etc. In Indian setup, home remedies are commonly used by the caregivers before visiting a dermatologist to treat various pediatric dermatoses.

Alopecia areata and isotretinoin; coincidence or causal relation.

Isotretinoin is a safe and useful medication for acne management. Adverse effects are mostly related to cutaneous and mucous membranes. We present a case of a 24-year-old female patient who was on treatment with isotretinoin for acne vulgaris Grade 4. After 6 months of treatment, the patient presented with localized patch of hair loss. Beginning of alopecia areata in patients with acne vulgaris could be regarded as a side effect of retinoids due to anti-acne therapy. The exact mechanism by which retinoids cause hair loss is not known.

Increased risk of angiosarcoma secondary to cancer radiotherapy: Case series and review of the treatment options.

Angiosarcomas (ASs) are aggressive tumors of vascular endothelial origin, occurring sporadically or in association with prior radiotherapy or chronic lymphedema. With only 1-5% of all sarcomas, the incidence seems low, but for the affected patient due to the extremely poor prognosis and the limited treatment options, the fate is often inevitable. Radiotherapy, chemotherapy, or "target therapy" have been used in the management of AS, but represent individual case decisions without lasting evidence. Over the past few years, breast-conserving surgery followed by radiation therapy, known as breast-conserving therapy (BCT), is being employed as a standard treatment for early-stage breast cancer, but there has been an increase in reports of AS following BCT. We report two cases of AS following BCT and one case of primary AS involving the lower limb.

Low dose of isotretinoin: A comprehensive review.

Isotretinoin is a first-generation retinoid initially approved for the treatment of severe cases of acne vulgaris (nodulocystic acne). Because of its broad anti-inflammatory and immunomodulatory properties, it has been used beyond its initial approval in a myriad of other indications. Adverse effects of isotretinoin vary from xerosis to teratogenicity. Herein, we reviewed the literature, through date-unlimited PubMed search, from inception till December 2019, using the following search terms: "low-dose isotretinoin" and "dermatology," "isotretinoin and safety," "isotretinoin, off-label uses," "isotretinoin and male fertility," "isotretinoin, iPLEDGE system," aiming to deliver a therapeutic update relevant to clinical practice. All English-language articles were considered with no limitation based on the articles' type. Low-dose isotretinoin is not limited to old and novel dermatological conditions, but also showed promising results in the field of infertility and safety in the field of gastroenterology. We also highlight on the safety profile of the drug and experts' recommendations to enhance safety measures to decrease fetal risk while on isotretinoin.

Complication of Soft Tissue Fillers: Prevention and Management Review.

The use of dermal fillers has increased manifold over the past decade, which has been attributed to the ever-increasing need of the population for being young. Fillers have become quite popular both among patients and treating physicians due to their quick and quite predictable results. Filler injection is a safe procedure in the hands of an experienced provider using appropriate technique. Nevertheless, various adverse effects to fillers have been reported that range from mild injection site complications, such as pain and bruising, to severe complications, like tissue necrosis, retinal artery occlusion, and infections. The esthetic provider should be aware of and be able to quickly recognize such complications, and be confident in managing them. In this article we highlight the various adverse effects noted with the use of fillers and discuss prevention and management. J Drugs Dermatol. 2020;19(9):829-832. doi:10.36849/JDD.2020.5084.

Parthenium dermatitis: is parthenolide an effective choice for patch testing?

BACKGROUND: Patch test positivity to parthenolide was observed less often than expected in strongly suspected cases of parthenium dermatitis after Chemotechnique Diagnostics (Sweden) replaced parthenium extract with parthenolide (0.5% pet.) by itself while marketing its Indian baseline series for patch testing. OBJECTIVE: The study was performed to find whether parthenolide detects parthenium contact sensitivity more effectively than parthenium extract in patients clinically presenting with classic parthenium dermatitis. MATERIAL AND METHODS: One hundred consecutive patients with suspected parthenium dermatitis were patch tested prospectively with the Indian baseline series, parthenium extract (1% aq.) and parthenolide (0.5% pet.) between July 2011 and April 2012. RESULTS: Only 37 of 100 patients with suspected parthenium dermatitis (male/female ratio of 20:17) reacted to parthenium extract (32 patients), parthenolide (17 patients), or both (12 patients). Reactions to parthenium extract were generally stronger than reactions to parthenolide. CONCLUSION: Patch testing with parthenolide (0.5% pet.) detects fewer cases of suspected parthenium dermatitis than patch testing with parthenium extract (1% aq.).

Berberine ameliorates glucocorticoid-induced hyperglycemia: an in vitro and in vivo study.

Berberine (BBR), a bioactive compound isolated from Coptidis Rhizoma, possesses diverse pharmacological activities including anti-bacterial, anti-inflammatory, antitumor, hypolipidemic, and anti-diabetic. However, its role as an anti-diabetic agent in animal models of dexamethasone (Dex)-induced diabetes remains unknown. Studies have shown that natural compounds including aloe, caper, cinnamon, cocoa, green and black tea, and turmeric can be used for treating Type 2 diabetes mellitus (DM). Compared to conventional drugs, natural compounds have less side effects and are easily available. Herein, we studied the anti-diabetic effects of BBR in a mice model of Dex-induced diabetes. HepG2 cell line was used for glucose release and glycogen synthesis studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. For animal studies, mice were treated with Dex (2 mg/kg, i.m.) for 30 days and effect of BBR at the doses 100, 200, and 500 mg/kg (p.o.) was analyzed. Glucose, insulin, and pyruvate tests were performed for evaluating the development of the diabetic model. Echo MRI was performed to assess the fat mass. Further, to elucidate the mechanism of action of BBR, mRNA expression of genes regulating gluconeogenesis, glucose uptake, and glycolysis was analyzed. In vitro BBR had no impact on cell viability up to a concentration of 50 µM. Moreover, BBR suppressed the hepatic glucose release and improved glucose tolerance in HepG2 cells. In vivo, BBR improved glucose homeostasis in diabetic mice as evidenced by enhanced glucose clearance, increased glycolysis, elevated glucose uptake, and decreased gluconeogenesis. Further, Dex treatment increased the total fat mass in mice, which was ameliorated by BBR treatment. BBR improves glucose tolerance by increasing glucose clearance, inhibiting hepatic glucose release, and decreasing obesity. Thus, BBR may become a potential therapeutic agent for treating glucocorticoid-induced diabetes and obesity in the future.

Molecular mechanisms underlying hyperglycemia associated cognitive decline.

Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia. DM can lead to a number of secondary complications affecting multiple organs in the body including the eyes, kidney, heart, and brain. The most common effect of hyperglycemia on the brain is cognitive decline. It has been estimated that 20-70% of people with DM have cognitive deficits. High blood sugar affects key brain areas involved in learning, memory, and spatial navigation, and the structural complexity of the brain has made it prone to a variety of pathological disorders, including T2DM. Studies have reported that cognitive decline can occur in people with diabetes, which could go undetected for several years. Moreover, studies on brain imaging suggest extensive effects on different brain regions in patients with T2D. It remains unclear whether diabetes-associated cognitive decline is a consequence of hyperglycemia or a complication that co-occurs with T2D. The exact mechanism underlying cognitive impairment in diabetes is complex; however, impaired glucose metabolism and abnormal insulin function are thought to play important roles. In this review, we have tried to summarize the effect of hyperglycemia on the brain structure and functions, along with the potential mechanisms underlying T2DM-associated cognitive decline.