Impaired Mitochondria Promote Aging-Associated Sebaceous Gland Dysfunction and Pathology.

Mitochondrial dysfunction is one of the hallmarks of aging. Changes in sebaceous gland (SG) function and sebum production have been reported during aging. This study shows the direct effects of mitochondrial dysfunction on SG morphology and function. A mitochondrial DNA (mtDNA) depleter mouse was used as a model for introducing mitochondrial dysfunction in the whole animal. The effects on skin SGs and modified SGs of the eyelid, lip, clitoral, and preputial glands were characterized. The mtDNA depleter mice showed gross morphologic and histopathologic changes in SGs associated with increased infiltration by mast cells, neutrophils, and polarized macrophages. Consistently, there was increased expression of proinflammatory cytokines. The inflammatory changes were associated with abnormal sebocyte accumulation of lipid, defective sebum delivery at the skin surface, and the up-regulation of key lipogenesis-regulating genes and androgen receptor. The mtDNA depleter mice expressed aging-associated senescent marker. Increased sebocyte proliferation and aberrant expression of stem cell markers were observed. These studies provide, for the first time, a causal link between mitochondrial dysfunction and abnormal sebocyte function within sebaceous and modified SGs throughout the whole body of the animal. They suggest that mtDNA depleter mouse may serve as a novel tool to develop targeted therapeutics to address SG disorders in aging humans.

Correction of MFG-E8 Resolves Inflammation and Promotes Cutaneous Wound Healing in Diabetes.

Milk fat globule epidermal growth factor-factor 8 (MFG-E8) is a peripheral glycoprotein that acts as a bridging molecule between the macrophage and apoptotic cells, thus executing a pivotal role in the scavenging of apoptotic cells from affected tissue. We have previously reported that apoptotic cell clearance activity or efferocytosis is compromised in diabetic wound macrophages. In this work, we test the hypothesis that MFG-E8 helps resolve inflammation, supports angiogenesis, and accelerates wound closure. MFG-E8(-/-) mice displayed impaired efferocytosis associated with exaggerated inflammatory response, poor angiogenesis, and wound closure. Wound macrophage-derived MFG-E8 was recognized as a critical driver of wound angiogenesis. Transplantation of MFG-E8(-/-) bone marrow to MFG-E8(+/+) mice resulted in impaired wound closure and compromised wound vascularization. In contrast, MFG-E8(-/-) mice that received wild-type bone marrow showed improved wound closure and improved wound vascularization. Hyperglycemia and exposure to advanced glycated end products inactivated MFG-E8, recognizing a key mechanism that complicates diabetic wound healing. Diabetic db/db mice suffered from impaired efferocytosis accompanied with persistent inflammation and slow wound closure. Topical recombinant MFG-E8 induced resolution of wound inflammation, improvements in angiogenesis, and acceleration of closure, upholding the potential of MFG-E8-directed therapeutics in diabetic wound care.

Epidermal E-Cadherin Dependent ß-Catenin Pathway Is Phytochemical Inducible and Accelerates Anagen Hair Cycling.

Unlike the epidermis, which regenerates continually, hair follicles anchored in the subcutis periodically regenerate by spontaneous repetitive cycles of growth (anagen), degeneration (catagen), and rest (telogen). The loss of hair follicles in response to injuries or pathologies such as alopecia endangers certain inherent functions of the skin. Thus, it is of interest to understand mechanisms underlying follicular regeneration in adults. In this work, a phytochemical rich in the natural vitamin E tocotrienol (TRF) served as a productive tool to unveil a novel epidermal pathway of hair follicular regeneration. Topical TRF application markedly induced epidermal hair follicle development akin to that during fetal skin development. This was observed in the skin of healthy as well as diabetic mice, which are known to be resistant to anagen hair cycling. TRF suppressed epidermal E-cadherin followed by 4-fold induction of ß-catenin and its nuclear translocation. Nuclear ß-catenin interacted with Tcf3. Such sequestration of Tcf3 from its otherwise known function to repress pluripotent factors induced the plasticity factors Oct4, Sox9, Klf4, c-Myc, and Nanog. Pharmacological inhibition of ß-catenin arrested anagen hair cycling by TRF. This work reports epidermal E-cadherin/ß-catenin as a novel pathway capable of inducing developmental folliculogenesis in the adult skin.

Mitochondria in Ovarian Aging and Reproductive Longevity.

Mitochondrial dysfunction is one of the hallmarks of aging. Consistently mitochondrial DNA (mtDNA) copy number and function decline with age in various tissues. There is increasing evidence to support that mitochondrial dysfunction drives ovarian aging. A decreased mtDNA copy number is also reported during ovarian aging. However, the mitochondrial mechanisms contributing to ovarian aging and infertility are not fully understood. Additionally, investigations into mitochondrial therapies to rejuvenate oocyte quality, select viable embryos and improve mitochondrial function may help enhance fertility or extend reproductive longevity in the future. These therapies include the use of mitochondrial replacement techniques, quantification of mtDNA copy number, and various pharmacologic and lifestyle measures. This review aims to describe the key evidence and current knowledge of the role of mitochondria in ovarian aging and identify the emerging potential options for therapy to extend reproductive longevity and improve fertility.

HISTOPATHOLOGICAL ANALYSIS OF SCHISTOSOMA HAEMATOBIUM METAPLASIA OF THE URINARY BLADDER.

The present cross sectional study was carried out to analyze the histopathological changes in the urinary bladder affected by Schistosoma haematobium among 54 patients (aged between 20-60 years; 40 males, 14 females; 44 from rural, 10 from urban areas) attending Sohag University Hospital, Egypt from. October 2015 to March 2016. 10% formalin fixed biopsy specimens were examined from which sections of 5 jum were prepared and examined microscopically. Mid-stream urine samples were collected from the patients after a slight physical exercise immediately transported to the Parasitological Laboratory to be examined for S. haematobium eggs. Histopathological examination revealed squamous metaplasia of the urinary bladder in 38/54 cases (70.4%); 20/54-(37%) non- keratinizing metaplasia, 18/54 (33.3%) keratinizing metaplasia and invasive squamous carcinoma in 11/54 (20.4%). It was concluded that Schistosonia haematobium is still one of the major risks of developing squamous cell metaplasia of the urinary bladder in Egypt which was found to be of high statistically significance in both males and females in rural areas. In this study, bladder squamous metaplasia was subdivided into non-keratinizing. with less malignant potential, keratinizing with a definite affinity to carcinogenesis and invasive severe forms; but these subdivisions were found to be statistically not significant in relation to gender, age and locality, although they were of importance for the proper and successful management of the encountered cases.

HISTOPATHOLOGICAL ANALYSIS OF SCHISTOSOMIASIS IN THE GASTROINTESTINAL TRACT WITH FIRST RECORD OF SCHISTOSOMAL APPENDICITIS FROM SOHAG, UPPER EGYPT.

Schistosomiasis is a chronic granulomatous inflammation that affects many systems in the body including the gastrointestinal tract. Appendiceal schistosomiasis is also described and can be a precursor lesion of schistosomal appendicitis. The present study was done to make a retrospective analysis of histopathological changes in the gastrointestinal tract affected by Sckistosoma mansoni among patients attending Sohag University Hospital, Sohag Governorate between June 2013 and June 2016. A total of 150 colon and 30 appendix specimens were collected through out the period from male infected pa- tients aged between 35-50 years and suffering from abdominal pain and dysentery. Histopathological examination of the tissue biopsies was performed. 5p tissue sections were prepared and examined microscopically. Ten specimens were documented to have intestinal schistosomiasis, nine of the colon 9/150 (6%) were diagnosed as chronic schistosomal colitis and one of the appendix 1/30 (3.3%) as chronic schistosomal appendicitis. Microphotographs of the tissue sections were prepared for histopathological observations. Histopathological examination of all specimens revealed degenerated pinkish and calcified bluish bilharzial eggs in the submucosa and even musculosa with surrounding granulomatous reaction. Bilharzial polyps of the colon were detected in two specimens (20%) and bilharzial worms within venules of the muscle layer in two specimens (20%). During the present study, S. mansoni was documented as a not uncommon cause of chronic colitis and for the first time from Sohag as a cause of chronic appendicitis. All specimens did not show any malignant or premalignant cells.

Genetically confirmed Fasciola hepatogigantica n.sp.

Identification of liver fluke species cannot be achieved by clinical, pathological, coprological or immunological methods. However, the differential diagnosis between F. hepatica and F. gigantica infection is very important because of their different pathological manifestations. Moreover, in countries where the two species co-exist, morphologically intermediate forms were reported. The present study aimed to identify these forms by the use of molecular characterization of DNA sequence. Based on morphometric criteria, adults of Fasciola hepatica, F. gigantica and intermediate forms were collected from naturally infected sheep and cattle from various regions of Sohag Governorate. A simple and rapid new method (QIAamp DNA Mini Kit) was used to isolate DNA from the worms and their RELP patterns were obtained after digestion of the PCR products with AvalI restriction enzymes. The result of a regular PCR experiment for the amplification of the selected 28S rDNA fragment with the designed primer set yielded identical 618- bp-long PCR products for the three types of Fasciola where the RFLP profile obtained from F. hepatica revealed four fragments of 628, 575, 165 and 95 bp, and F. gigantica generated three fragments corresponding to 628, 358 and 300 bp fragments whereas the intermediate forms revealed four fragments of 628, 541, 358 and 300 bp, which were similar to those ofF. gigantica but with a distinctive fragment of 541. These results confirmed that three species are present in our locality: F. hepatica, F. gigantica and an intermediate form which was named F. hepatogigantica n.sp. on basis of having few morphometric characters from F. hepatica (length and pattern of uterine coils) but genetically they were more related to F. gigantica.

Consumption hazards of cattle liver infected with Fasciola spp.: II. Experimental study on rats.

This study evaluated and revealed the consumption hazards of cattle liver infected with Fasciola spp. and revealed its effects on the serum estimation of liver enzyme (ALT) on experimental rats. A total of42 Wister albino rats were classified into 7 groups. Four groups were fed on raw and cooked cattle liver with various intensity of Fasciola spp. infection. Two groups were fed on raw and cooked normal cattle liver (positive control), and one group served as negative control. Histopathology of the rats' liver revealed hydropic degeneration, congestion with dilatation of the central vein and sinusoids and focal areas of necrosis. The intestine samples showed degenerative changes and necrobiosis of the villar epithelium with inflammatory cell infiltration. Moreover, a slight increase was noticed in the liver enzyme ALT which is known to be an important marker of liver destruction.