Genetic-informed proteome-wide scan reveals potential causal plasma proteins for idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease for which there are no reliable biomarkers or disease-modifying drugs. Here, we integrated human genomics and proteomics to investigate the causal associations between 2769 plasma proteins and IPF. Our Mendelian randomisation analysis identified nine proteins associated with IPF, of which three (FUT3, ADAM15 and USP28) were colocalised. ADAM15 emerged as the top candidate, supported by expression quantitative trait locus analysis in both blood and lung tissue. These findings provide novel insights into the aetiology of IPF and offer translational opportunities in response to the clinical challenges of this devastating disease.

A genetically informed study reveals modifiable pathways in skin cancer.

BACKGROUND: Identifying modifiable risk factors is essential for the prevention of skin cancer; however, establishing causality can be challenging in conventional epidemiological studies. This study aimed to determine the causal associations of potentially modifiable risk factors with skin cancer using Mendelian randomization (MR). METHODS: Genetic instruments for 53 risk factors, including socioeconomic status, dietary and lifestyle factors, anthropometric measures, medication use, and comorbidities, were identified from previous genome-wide association studies. Two-sample MR analyses were performed using summary statistics for three major types of skin cancer: melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Findings were verified using multiple MR methods under different assumptions and replication datasets. RESULTS: Genetic liability to sunburn occasions, actinic keratosis, and prior skin cancers was associated with a higher risk of all three types of skin cancer, whereas genetic liability to vitiligo was associated with a lower risk. For specific skin cancer types, genetically predicted higher nevus counts and occupational class were associated with an increased risk of melanoma. Genetic liability to rheumatoid arthritis, type 2 diabetes, and increased physical activity were associated with a lower risk of BCC. Genetically predicated body mass index showed a negative association with BCC, and a positive association with SCC. CONCLUSIONS: Our study reaffirmed several previously established risk factors and identified novel potential risk factors for skin cancer. Further work is needed to unravel the biological pathways in different skin cancer types and translate our findings to inform public health policies.

Impact of genetically predicted characterization of mitochondrial DNA quantity and quality on osteoarthritis.

Background: Existing studies have indicated that mitochondrial dysfunction may contribute to osteoarthritis (OA) development. However, the causal association between mitochondrial DNA (mtDNA) characterization and OA has not been extensively explored. Methods: Two-sample Mendelian randomization was performed to calculate the impact of mitochondrial genomic variations on overall OA as well as site-specific OA, with multiple analytical methods inverse variance weighted (IVW), weighted median (WM), MR-Egger and MR-robust adjusted profile score (MR-RAPS). Results: Genetically determined mitochondrial heteroplasmy (MtHz) and mtDNA abundance were not causally associated with overall OA. In site-specific OA analyses, the causal effect of mtDNA abundance on other OA sites, including hip, knee, thumb, hand, and finger, had not been discovered. There was a suggestively protective effect of MtHz on knee OA IVW OR = 0.632, 95% CI: 0.425-0.939, p-value = 0.023. No causal association between MtHz and other different OA phenotypes was found. Conclusion: MtHz shows potential to be a novel therapeutic target and biomarker on knee OA development. However, the variation of mtDNA abundance was measured from leukocyte in blood and the levels of MtHz were from saliva samples rather than cartilage or synovial tissues. Genotyping samples from synovial and cartilage can be a focus to further exploration.

Rosacea Aggravated after Intracutaneous Injection of Poly-L-lactic Acid through a Stamp-type Microneedle.

Injectable poly-L-lactic acid (PLLA) has been widely used for skin texture improvement, volume augmentations of the face or body, and other cosmetic or reconstructive treatment. Despite its significant efficacy, many side effects have also been reported. Here, we describe a case of rosacea aggravated by intracutaneous injection of PLLA using a mesogun injector with stamp-type microneedle. After the treatment, the patient exhibited aggravated rosacea symptoms, such as flushing and erythema. A possible mechanism for the exacerbations might be that PLLA stimulated subclinical inflammatory reaction in the skin. We suggest that PLLA injection should be administered more cautiously in patients with rosacea or other inflammatory skin lesions.

Mechanism of action and therapeutic effects of oxidative stress and stem cell-based materials in skin aging: Current evidence and future perspectives.

Aging is associated with multiple degenerative diseases, including atherosclerosis, osteoporosis, and Alzheimer's disease. As the most intuitive manifestation of aging, skin aging has received the most significant attention. Skin aging results from various intrinsic and extrinsic factors. Aged skin is characterized by wrinkles, laxity, elastosis, telangiectasia, and aberrant pigmentation. The underlying mechanism is complex and may involve cellular senescence, DNA damage, oxidative stress (OS), inflammation, and genetic mutations, among other factors. Among them, OS plays an important role in skin aging, and multiple antioxidants (e.g., vitamin C, glutathione, and melatonin) are considered to promote skin rejuvenation. In addition, stem cells that exhibit self-replication, multi-directional differentiation, and a strong paracrine function can exert anti-aging effects by inhibiting OS. With the further development of stem cell technology, treatments related to OS mitigation and involving stem cell use may have a promising future in anti-skin aging therapy.

Fibroblasts in Scar Formation: Biology and Clinical Translation.

Scarring, which develops due to fibroblast activation and excessive extracellular matrix deposition, can cause physical, psychological, and cosmetic problems. Fibroblasts are the main type of connective tissue cells and play important roles in wound healing. However, the underlying mechanisms of fibroblast in reaching scarless wound healing require more exploration. Herein, we systematically reviewed how fibroblasts behave in response to skin injuries, as well as their functions in regeneration and scar formation. Several biocompatible materials, including hydrogels and nanoparticles, were also suggested. Moreover, factors that concern transformation from fibroblasts into cancer-associated fibroblasts are mentioned due to a tight association between scar formation and primary skin cancers. These findings will help us better understand skin fibrotic pathogenesis, as well as provide potential targets for scarless wound healing therapies.