Aging in the dermis: Fibroblast senescence and its significance.

Skin aging is characterized by changes in its structural, cellular, and molecular components in both the epidermis and dermis. Dermal aging is distinguished by reduced dermal thickness, increased wrinkles, and a sagging appearance. Due to intrinsic or extrinsic factors, accumulation of excessive reactive oxygen species (ROS) triggers a series of aging events, including imbalanced extracellular matrix (ECM) homeostasis, accumulation of senescent fibroblasts, loss of cell identity, and chronic inflammation mediated by senescence-associated secretory phenotype (SASP).

Stratum corneum hydration inversely correlates with certain serum cytokine levels in the elderly, possibly contributing to inflammaging.

Background: Chronic, low-grade inflammation, also termed 'inflammaging', has been linked to the development of some aging-associated disorders. Recent studies suggest that inflammaging is attributable to aging-associated epidermal dysfunction. However, abnormality in which epidermal function contributes to inflammaging is not clear.

Highlights from the 24th workshop on vitamin D in Austin, September 2022.

The 24th Workshop on Vitamin D was held September 7-9, 2022 in Austin, Texas and covered a wide diversity of research in the vitamin D field from across the globe. Here, we summarize the meeting, individual sessions, awards and presentations given.

A topical emollient mitigates the progression of cognitive impairment in the elderly: a randomized, open-label pilot trial.

Background: Cognitive impairment is common in the elderly. Prior studies suggest a link between chronic inflammation and cognitive dysfunction, while aging-associated epidermal dysfunction has been connected to elevations in circulating cytokines.

Objective: We assessed here whether improvements in epidermal function can mitigate the progression of cognitive impairment.

Transcriptional Regulation of Dental Epithelial Cell Fate.

Dental enamel is hardest tissue in the body and is produced by dental epithelial cells residing in the tooth. Their cell fates are tightly controlled by transcriptional programs that are facilitated by fate determining transcription factors and chromatin regulators. Understanding the transcriptional program controlling dental cell fate is critical for our efforts to build and repair teeth.

Deletion of Mediator 1 suppresses TGFβ signaling leading to changes in epidermal lineages and regeneration.

Epidermal lineages and injury induced regeneration are controlled by transcriptional programs coordinating cellular signaling and epigenetic regulators, but the mechanism remains unclear. Previous studies showed that conditional deletion of the transcriptional coactivator Mediator 1 (Med1) changes epidermal lineages and accelerates wound re-epithelialization. Here, we studied a molecular mechanism by which Med1 facilitates these processes, in particular, by focusing on TGFβ signaling through genome wide transcriptome analysis.

Role of Resveratrol in Regulating Cutaneous Functions.

Protective role of the skin is against external insults and maintenance of electrolyte homeostasis of the body. Cutaneous dysfunction can account for the development of both cutaneous and systemic disorders. Thus, improvements in cutaneous functions can benefit a number of extracutaneous and cutaneous functions.

Altered Epidermal Permeability Barrier Function in the Uninvolved Skin Supports a Role of Epidermal Dysfunction in the Pathogenesis of Occupational Hand Eczema.

Although a compromised epidermal permeability barrier can contribute to the development of contact dermatitis, whether subjects with hand eczema display abnormalities in baseline epidermal permeability barrier function in their uninvolved skin remains unknown. The aim of the present study was to assess epidermal permeability barrier function in subjects with and without hand eczema in clothing manufacturers. Upon approval by the institutional review board, volunteers were recruited from clothing manufacturers in Guangzhou City, China.

Aging-associated alterations in epidermal function and their clinical significance.

Chronologically-aged skin displays multiple functional changes in both the dermis and the epidermis. It appears that epidermal dysfunction, compromised permeability homeostasis, reduced stratum corneum hydration and elevated skin surface pH predispose to the development of aging-associated cutaneous and extracutaneous disorders. Improvements in epidermal function have been shown to be an effective alternative therapy in the prevention and treatment of some aging-associated cutaneous disorders, including eczematous dermatitis, pruritus, and xerosis.

The Fracture Callus Is Formed by Progenitors of Different Skeletal Origins in a Site-Specific Manner.

We evaluated repair following a mid-diaphyseal fracture of the tibia in 3-month-old mice. We observed differences in the repair process at three different sites of the callus. Site 1: bone developing from the outer layer of the periosteum of the cortex; site 2: bone developing within the bridge/central region of the fracture; and site 3: bone developing within the marrow of the ends of broken bones.

Benefits of Hesperidin for Cutaneous Functions.

Hesperidin is a bioflavonoid, with high concentration in citrus fruits. In addition to its well-known benefits for cardiovascular function, type II diabetes, and anti-inflammation, recent studies have demonstrated multiple benefits of hesperidin for cutaneous functions, including wound healing, UV protection, anti-inflammation, antimicrobial, antiskin cancer, and skin lightening. In addition, hesperidin enhances epidermal permeability barrier homeostasis in both normal young and aged skin.

Lasers for Becker's nevus.

Becker's nevus is a common pigmented dermatosis, usually featured by ipsilateral pigmented patch with hypertrichosis. Becker's nevus is often treated with various types of lasers although other regimens are available. However, clinical outcomes appear inconsistent among studies.

Comment on: The Vitamin D⁻Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas, 2018, , 554.

In response to a recent article by Jones et al. (Nutrients 10: 554⁻568, 2018) [1], we agree that three distinctive features evolved in Homo erectus prior to the emergence of modern humans.[.

EAAC1 gene deletion reduces adult hippocampal neurogenesis after transient cerebral ischemia.

Several studies have demonstrated that excitatory amino acid carrier-1 (EAAC1) gene deletion exacerbates hippocampal and cortical neuronal death after ischemia. However, presently there are no studies investigating the role of EAAC1 in hippocampal neurogenesis. In this study, we tested the hypothesis that reduced cysteine transport into neurons by EAAC1 knockout negatively affects adult hippocampal neurogenesis under physiological or pathological states.

Engineered Exosomes as Vehicles for Biologically Active Proteins.

Exosomes represent an attractive vehicle for the delivery of biomolecules. However, mechanisms for loading functional molecules into exosomes are relatively unexplored. Here we report the use of the evolutionarily conserved late-domain (L-domain) pathway as a mechanism for loading exogenous proteins into exosomes.

Apolipoprotein E enhances microRNA-146a in monocytes and macrophages to suppress nuclear factor-κB-driven inflammation and atherosclerosis.

Rationale: Apolipoprotein E (apoE) exerts anti-inflammatory properties that protect against atherosclerosis and other inflammatory diseases. However, mechanisms by which apoE suppresses the cellular activation of leukocytes commonly associated with atherosclerosis remain incompletely understood.

Objective: To test the hypothesis that apoE suppresses inflammation and atherosclerosis by regulating cellular microRNA levels in these leukocytes.

Calcium-sensing receptor (CaSR) as a novel target for ischemic neuroprotection.

Object: Ischemic brain injury is the leading cause for death and long-term disability in patients who suffer cardiac arrest and embolic stroke. Excitotoxicity and subsequent Ca(2+)-overload lead to ischemic neuron death. We explore a novel mechanism concerning the role of the excitatory extracellular calcium-sensing receptor (CaSR) in the induction of ischemic brain injury.

Ablation of coactivator Med1 switches the cell fate of dental epithelia to that generating hair.

Cell fates are determined by specific transcriptional programs. Here we provide evidence that the transcriptional coactivator, Mediator 1 (Med1), is essential for the cell fate determination of ectodermal epithelia. Conditional deletion of Med1 in vivo converted dental epithelia into epidermal epithelia, causing defects in enamel organ development while promoting hair formation in the incisors.

Prevention of hypoglycemia-induced neuronal death by minocycline.

Diabetic patients who attempt strict management of blood glucose levels frequently experience hypoglycemia. Severe and prolonged hypoglycemia causes neuronal death and cognitive impairment. There is no effective tool for prevention of these unwanted clinical sequelae.

EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia.

EAAC1 is a neuronal glutamate and cysteine transporter. EAAC1 uptake of cysteine provides substrate for neuronal glutathione synthesis, which plays a key role in both antioxidant defenses and intracellular zinc binding. Here we evaluated the role of EAAC1 in neuronal resistance to ischemia.

Epigenetics of prostate cancer.

Prostate cancer is the most common type of cancer other than skin cancer and the second leading cause of cancer death in men in the United States. Its exact causes are unknown. Several risk factors have been associated with prostate cancer including age, race, family history and diet.

Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrations.

Poly(ADP-ribose) polymerase-1 (PARP-1), when activated by DNA damage, promotes both cell death and inflammation. Here we report that PARP-1 enzymatic activity is directly inhibited by minocycline and other tetracycline derivatives that have previously been shown to have neuroprotective and anti-inflammatory actions. These agents were evaluated by using cortical neuron cultures in which PARP-1 activation was induced by the genotoxic agents N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or 3-morpholinosydnonimine (SIN-1).

WT1 and WT1-AS genes are inactivated by promoter methylation in ovarian clear cell adenocarcinoma.

Background: Ovarian clear cell adenocarcinoma is associated with one of the poorest prognoses among human epithelial ovarian cancers. The authors hypothesized that Wilms tumor suppressor 1 gene (WT1) sense and antisense (WT1-AS) expression and their promoter methylation status could characterize ovarian clear cell adenocarcinoma from ovarian serous adenocarcinoma.

Methods: To test this hypothesis, ovarian cancer cell lines and 42 cancer tissues (17 clear cell and 25 serous adenocarcinoma) were analyzed for expression and methylation of WT1 and WT1-AS genes.