Autophagy (self-eating) is a conserved cellular degradation process that plays important roles in maintaining homeostasis and preventing nutritional, metabolic, and infection-mediated stresses. Autophagy dysfunction can have various pathological consequences, including tumor progression, pathogen hyper-virulence, and neurodegeneration. This review describes the mechanisms of autophagy and its associations with other cell death mechanisms, including apoptosis, necrosis, necroptosis, and autosis. Autophagy has both positive and negative roles in infection, cancer, neural development, metabolism, cardiovascular health, immunity, and iron homeostasis. Genetic defects in autophagy can have pathological consequences, such as static childhood encephalopathy with neurodegeneration in adulthood, Crohn’s disease, hereditary spastic paraparesis, Danon disease, X-linked myopathy with excessive autophagy, and sporadic inclusion body myositis. Further studies on the process of autophagy in different microbial infections could help to design and develop novel therapeutic strategies against important pathogenic microbes. This review on the progress and prospects of autophagy research describes various activators and suppressors, which could be used to design novel intervention strategies against numerous diseases and develop therapeutic drugs to protect human and animal health.

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A Comprehensive Review of Autophagy and Its Various Roles in Infectious, Non-Infectious, and Lifestyle Diseases: Current Knowledge and Prospects for Disease Prevention, Novel Drug Design, and Therapy.

Microneedle arrays (MNA) are considered as one of the most promising resources to achieve systemic effects by transdermal delivery of drugs. They are designed as a minimally invasive, painless system which can bypass the stratum corneum, overcoming the potential drawbacks of subcutaneous injections and other transdermal delivery systems such as chemical enhancers, nano and microparticles, or physical treatments. As a trendy field in pharmaceutical and biomedical research, its applications are constantly evolving, even though they are based on very well-established techniques. The number of molecules administered by MNA are also increasing, with insulin and vaccines administration being the most investigated. Furthermore, MNA are being used to deliver cells and applied in other organs and tissues like the eyes and buccal mucosae. This review intends to offer a general overview of the current state of MNA research, focusing on the strategies, applications, and types of molecules delivered recently by these systems. In addition, some information about the materials and manufacturing processes is presented and safety data is discussed.

Microneedle-Based Delivery: An Overview of Current Applications and Trends

Hyperhidrosis (HH) is a chronic disorder of excess sweat production that may have a significant adverse effect on quality of life. A variety of treatment modalities currently exist to manage HH. Initial treatment includes lifestyle and behavioral recommendations. Antiperspirants are regarded as the first-line therapy for primary focal HH and can provide significant benefit. Iontophoresis is the primary remedy for palmar and plantar HH. Botulinum toxin injections are administered at the dermal-subcutaneous junction and serve as a safe and effective treatment option for focal HH. Oral systemic agents are reserved for treatment-resistant cases or for generalized HH. Energy-delivering devices such as lasers, ultrasound technology, microwave thermolysis, and fractional microneedle radiofrequency may also be utilized to reduce focal sweating. Surgery may be considered when more conservative treatments have failed. Local surgical techniques, particularly for axillary HH, include excision, curettage, liposuction, or a combination of these techniques. Sympathectomy is the treatment of last resort when conservative treatments are unsuccessful or intolerable, and after accepting secondary compensatory HH as a potential complication. A review of treatment modalities for HH and a sequenced approach are presented.

The etiology, diagnosis, and management of hyperhidrosis: A comprehensive review: Therapeutic options

Paradoxically, trichothecenes have both immunosuppressive and immunostimulatory effects. The underlying mechanisms have not been fully explored. Early studies show that dose, exposure timing, and the time at which immune function is assessed influence whether trichothecenes act in an immunosuppressive or immunostimulatory fashion. Recent studies suggest that the immunomodulatory function of trichothecenes is also actively shaped by competing cell-survival and death-signaling pathways. Autophagy may also promote trichothecene immunosuppression, although the mechanism may be complicated. Moreover, trichothecenes may generate an “immune evasion” milieu that allows pathogens to escape host and vaccine immune defenses. Some trichothecenes, especially macrocyclic trichothecenes, also potently kill cancer cells. T-2 toxin conjugated with anti-cancer monoclonal antibodies significantly suppresses the growth of thymoma EL-4 cells and colon cancer cells. The type B trichothecene diacetoxyscirpenol specifically inhibits the tumor-promoting factor HIF-1 in cancer cells under hypoxic conditions. Trichothecin markedly inhibits the growth of multiple cancer cells with constitutively activated NF-κB. The type D macrocyclic toxin Verrucarin A is also a promising therapeutic candidate for leukemia, breast cancer, prostate cancer, and pancreatic cancer. The anti-cancer activities of trichothecenes have not been comprehensively summarized. Here, we first summarize the data on the immunomodulatory effects of trichothecenes and discuss recent studies that shed light on the underlying cellular and molecular mechanisms. These mechanisms include autophagy and major signaling pathways and their crosstalk. Second, the anti-cancer potential of trichothecenes and the underlying mechanisms will be discussed. We hope that this review will show how trichothecene bioactivities can be exploited to generate therapies against pathogens and cancer.

Trichothecenes: immunomodulatory effects, mechanisms, and anti-cancer potential

Hyperhidrosis is defined as the production of sweat beyond what is physiologically necessary to maintain thermal homeostasis This disease state may (and typically does) have a significant impact on the patient's quality of life Medications including antiperspirants, anticholinergics, and botulinum toxin have been shown to be effective in the management of hyperhidrosis Several medical device technologies have also proven to be effective This review article will explore the current and emerging pharmacological and medical device treatments for hyperhidrosis and provide a framework for treating patients who suffer with primary forms of hyperhidrosis

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Current and Emerging Medical Therapies for Primary Hyperhidrosis.

Autophagy, literally meaning "self-eating," is an intracellular catabolic process of delivering cytosol and/or its specific content to the lysosomes for degradation.The resulting macromolecular constituents are recycled and utilized again by the cells. Basal level autophagy plays an important role in cellular homeostasis through the elimination of the old or damaged organelles, as well as aggregated intracellular proteins. Autophagy refers to sequestration of intact organelles along with a portion of cytosol, into a double-or multi-membrane structure known as phagophore, which elongates, and after closure, forms a vesicular structure known as the autophagosome. Subsequently, the mature autophagosome fuses with a lysosome, thereby forming a single membrane structure, an autolysosome. Autophagy plays a critical role in inflammation, autoimmunity and cellular differentiation. Skin serves as the first line of defense against a variety of environmental insults and autophagy is thought to be a form of an endogenous defense mechanism against such environmental derangements. Autophagy has been linked with keratinocyte differentiation and melanocyte survival, as well as with the pathogenesis of diverse skin disorders including systemic lupus erythematosus, systemic sclerosis, psoriasis, vitiligo, infectious skin diseases and cancer. Autophagy has been one of the most studied phenomena in cell biology and pathophysiology, and given its broad clinical implications, has become a major target for drug discovery. The last decade has seen a substantial upsurge in autophagy-related research and publications; still, the dermatology literature appears to be less initiated. Autophagy will probably change our understanding of dermatological disorders/medicines. Hence, a basic knowledge of autophagy is a prerequisite to understand the developments in the field of autophagy-related research.

Autophagy: A brief overview in perspective of dermatology

Iontophoresis is defined as passing of an ionized substance through intact skin by application of direct electric current. Tap water iontophoresis is reliable and effective method for treatment of palmar and plantar hyperhydrosis when practiced with appropriate technique and timing. One of the major setback for using iontophoresis is that the apparatus is expensive and is not readily available. A simple user-made Iontophoresis device have been described here, which could be easily constructed and used at home.

A Simple User-made Iontophoresis Device for Palmoplantar Hyperhidrosis.

Background: Onychomycosis is one of the most common nail disorders. Mycological examination by potassium hydroxide (KOH) mount and fungal culture is the most commonly used diagnostic method. However, it is associated with a low sensitivity. Aims: To evaluate the technique of subungual hyperkeratosis nail biopsy in diagnosing onychomycosis in HIV-infected and immunocompetent adults and compare it with mycological examination. Methods: 34 HIV-positive patients who presented clinically with onychomycosis were recruited in the study from the beginning. There was no screening done for patients with onychomycosis. This has been clarified in manuscript under the heading of methods. Results: All the fungal cultures yielded dermatophytes correlating with the biopsy findings. Only hyphal form of fungus was detected in KOH examination, indicating it was not a contaminant. Clinical types of onychomycosis are stated in discussion. Conclusions: PAS stain of subungual hyperkeratosis nail biopsy was the most sensitive in the diagnosis of onychomycosis in both HIV-infected and non-infected groups.

Subungual hyperkeratosis nail biopsy: a better diagnostic tool for onychomycosis.

INTRODUCTION Although the tests could be done at any site, the proximal part of the flexor aspect of the forearm is Intradermal tests are widely used to support the conventionally used. This site can be conveniently diagnosis of dermatological and nondermatological exposed and the skin of the proximal area is more diseases. They are mainly indicated for the detection sensitive than the distal. of immediate (Type I hypersensitivity) and delayed type hypersensitivity (DTH, Type IV hypersensitivity) INTERPRETATION OF INTRADERMAL TESTS towards exogenous or endogenous antigens. Intradermal tests for the diagnosis of infectious The optimal time for reading the reaction depends diseases in relevance to dermatovenereology are upon the pharmacological agent used for the test discussed in this section. and the type of immunological reaction to be observed. Intradermal tests for the detection of DTH Intradermal tests for the diagnosis of infectious are read at 48h, although they can be read as early diseases are listed in Table 1. They are indicated to as 12h and as late as four days. (The lepromin test detect DTH to organisms or their antigens. is read at four weeks and depends on the formation of a granuloma, which is a measure of cell-mediated Before undertaking intradermal test, it is advisable to immunity.) The size of the induration is more stop or avoid systemic steroids or immunosuppressive important than erythema while interpreting Type agents at least three days before the procedure as IV hypersensitivity. moderate to large doses of corticosteroids may inhibit a DTH reaction.

Intradermal tests in dermatology-I: tests for infectious diseases.

Background: Trichoscopy is a reliable instrument for diagnosis and for tracking therapy-related changes in female pattern hair loss (FPHL). Videodermoscopic diagnosis of FPHL has been established, which requires fine measurements of hair-related parameters; the method requires an expensive equipment/digital program. Aim: To determine whether a low-cost, simple USB dermoscope can ascertain the hair-related changes in early FPHL. Methods: An age-matched, cross-sectional study was performed over 3 years on subjects with less than 6-month history of hair loss and without an obvious broadening of midline hair parting. Trichoscopic analysis of the frontal and occipital scalp of the study subjects were performed, using a USB-connected dermoscope. The subjects were analyzed for the presence of microscopic hair changes in the form of anisotrichosis, vellus-like hair, single hair follicle unit, peri-pilar sign and yellow dots. Results: A total of 230 cases and 230 controls were analyzed. The dermoscopic hair changes were found to be significantly associated with the frontal scalp zone of cases. Limitations: Histopathological evaluation of the cases was not done. Conclusion: Microscopic changes recorded with the help of a simple USB dermoscope are helpful in establishing a diagnosis of FPHL even in early disease.

Rahul Nagar

Papers

Autophagy: A brief overview in perspective of dermatology

A Simple User-made Iontophoresis Device for Palmoplantar Hyperhidrosis.

Subungual hyperkeratosis nail biopsy: a better diagnostic tool for onychomycosis.

Intradermal tests in dermatology-I: tests for infectious diseases.

Utility of trichoscopy to diagnose early female pattern hair loss in resource-poor setting: A cross-sectional study.