Transpiration-Inspired Fabric Dressing for Acceleration Healing of Wound Infected with Biofilm.

In chronic wound management, efficacious handling of exudate and bacterial infections stands as a paramount challenge. Here we introduced a novel biomimetic fabric, inspired by the natural transpiration mechanisms in plants. Uniquely, the fabric combines a commercial polyethylene terephthalate (PET) fabric with asymmetrically grown 1D rutile titanium dioxide (TiO2) micro/nanostructures, emulating critical plant features: hierarchically porous networks and hydrophilic water conduction channels. This structure endows the fabric with exceptional antigravity wicking-evaporation performance, evidenced by a 780% one-way transport capability and a 0.75 g h-1 water evaporation rate, which significantly surpasses that of conventional moisture-wicking textiles. Moreover, the incorporated 1D rutile TiO2 micro/nano-structures presented solar-light induced antibacterial activity, crucial for disrupting and eradicating wound biofilms. The biomimetic transpiration fabric has been employed to drain exudate and eradicate biofilms in Staphylococcus aureus (S. aureus)-infected wounds, demonstrating a much faster infection eradication capability compared to clinically common ciprofloxacin irrigation. These findings illuminate the path for developing high-performance, textile-based wound dressings, offering efficient clinical platforms to combat biofilms associated with chronic wounds. This article is protected by copyright. All rights reserved.

ELABELA-derived peptide ELA13 attenuates kidney fibrosis by inhibiting the Smad and ERK signaling pathways. / ELABELA衍生肽ELA13通过抑制Smad和ERK信号通路减轻肾纤维化.

Kidney fibrosis is an inevitable result of various chronic kidney diseases (CKDs) and significantly contributes to end-stage renal failure. Currently, there is no specific treatment available for renal fibrosis. ELA13 (amino acid sequence: RRCMPLHSRVPFP) is a conserved region of ELABELA in all vertebrates; however, its biological activity has been very little studied. In the present study, we evaluated the therapeutic effect of ELA13 on transforming growth factor-ß1 (TGF-ß1)-treated NRK-52E cells and unilateral ureteral occlusion (UUO) mice. Our results demonstrated that ELA13 could improve renal function by reducing creatinine and urea nitrogen content in serum, and reduce the expression of fibrosis biomarkers confirmed by Masson staining, immunohistochemistry, real-time polymerase chain reaction (RT-PCR), and western blot. Inflammation biomarkers were increased after UUO and decreased by administration of ELA13. Furthermore, we found that the levels of essential molecules in the mothers against decapentaplegic (Smad) and extracellular signal-regulated kinase (ERK) pathways were reduced by ELA13 treatment in vivo and in vitro. In conclusion, ELA13 protected against kidney fibrosis through inhibiting the Smad and ERK signaling pathways and could thus be a promising candidate for anti-renal fibrosis treatment.

Advances in the research and application of neurokinin-1 receptor antagonists. / 神经激肽1å—ä½“æ‹®æŠ—å‰‚çš„ç ”ç©¶ä¸Žåº”ç”¨è¿›å±•.

Recently, the substance P (SP)/neurokinin-1 receptor (NK-1R) system has been found to be involved in various human pathophysiological disorders including the symptoms of coronavirus disease 2019 (COVID-19). Besides, studies in the oncological field have demonstrated an intricate correlation between the upregulation of NK-1R and the activation of SP/NK-1R system with the progression of multiple carcinoma types and poor clinical prognosis. These findings indicate that the modulation of SP/NK-1R system with NK-1R antagonists can be a potential broad-spectrum antitumor strategy. This review updates the latest potential and applications of NK-1R antagonists in the treatment of human diseases and cancers, as well as the underlying mechanisms. Furthermore, the strategies to improve the bioavailability and efficacy of NK-1R antagonist drugs are summarized, such as solid dispersion systems, nanonization, and nanoencapsulation. As a radiopharmaceutical therapeutic, the NK-1R antagonist aprepitant was originally developed as radioligand receptor to target NK-1R-overexpressing tumors. However, combining NK-1R antagonists with other drugs can produce a synergistic effect, thereby enhancing the therapeutic effect, alleviating the symptoms, and improving patients quality of life in several diseases and cancers.

[Latest Findings on Long Noncoding RNA in Tumor Microenvironment].

Tumor microenvironment incorporates various tumor-related cellular and non-cellular components, playing a crucial role in the process of the pathogenesis, growth, and metastasis of tumors. Long noncoding RNA (lncRNA), a kind of noncoding RNA with a length of more than 200 nt, participates in a variety of physiological and pathological processes. Recent studies have shown that lncRNA plays a vital role in the interaction between tumors and the tumor microenvironment, thereby affecting tumor progression. Herein, we reviewed the research progress on the lncRNA in tumor microenvironment, discussed the potential application of lncRNA in early diagnosis and treatment of tumors, and suggested that some issues should be further explored in future research, including developing effective strategies for knocking out specific lncRNA and selecting appropriate in vivo delivery vehicles targeting specific cells.

Association of a single amino acid replacement with dorsal pigmentation in a lizard from the Qinghai-Tibetan Plateau.

Reptiles can evolve adaptive colors in different environments, but relatively little is known about the genetic mechanisms. Here, we identified the MC1R gene and its association with intraspecific color variation in the lizard Phrynocephalus erythrurus. Analysis of the MC1R sequence in 143 individuals from dark South Qiangtang Plateau (SQP) and light North Qiangtang plateau (NQP) populations, revealed two amino acid sites that showed significant differences in frequency between two areas. One SNP, corresponding to Glu183Lys residue, was found to be a highly significant outlier and differentially fixed for SQP and NQP populations. This residue is located in an extracellular area in the second small extracellular loop within the secondary structure of MC1R, which represents an "attachment pocket" part of the 3D structure. Cytological expression of MC1R alleles with the Glu183Lys replacement showed a 39 % increase in intracellular agonist-induced cyclic AMP levels and a 23.18 % greater cell surface expression of MC1R protein in the SQP relative to the NQP allele. Further in silico 3D modeling and in vitro binding experiments indicated a higher MC1R-α-MSH binding for the SQP allele, and elevated melanin synthesis. We provide an overview of how a single amino acid replacement leads to fundamental changes in MC1R function, and hence shapes variation in dorsal pigmentation in lizards from different environments.

Targeting Annexin A1 as a Druggable Player to Enhance the Anti-Tumor Role of Honokiol in Colon Cancer through Autophagic Pathway.

Colon cancer is one of the most common digestive tract malignancies, having the second highest mortality rate among all tumors, with a five-year survival of advanced patients of only 10%. Efficient, targeted drugs are still lacking in treating colon cancer, so it is urgent to explore novel druggable targets. Here, we demonstrated that annexin A1 (ANXA1) was overexpressed in tumors of 50% of colon cancer patients, and ANXA1 overexpression was significantly negatively correlated with the poor prognosis of colon cancer. ANXA1 promoted the abnormal proliferation of colon cancer cells in vitro and in vivo by regulating the cell cycle, while the knockdown of ANXA1 almost totally inhibited the growth of colon cancer cells in vivo. Furthermore, ANXA1 antagonized the autophagic death of honokiol in colon cancer cells via stabilizing mitochondrial reactive oxygen species. Based on these results, we speculated that ANXA1 might be a druggable target to control colon cancer and overcome drug resistance.

Therapeutic potential for targeting Annexin A1 in fibrotic diseases.

Annexin A1, a well-known endogenous anti-inflammatory mediator, plays a critical role in a variety of pathological processes. Fibrosis is described by a failure of tissue regeneration and contributes to the development of many diseases. Accumulating evidence supports that Annexin A1 participates in the progression of tissue fibrosis. However, the fundamental mechanisms by which Annexin A1 regulates fibrosis remain elusive, and even the functions of Annexin A1 in fibrotic diseases are still paradoxical. This review focuses on the roles of Annexin A1 in the development of fibrosis of lung, liver, heart, and other tissues, with emphasis on the therapy potential of Annexin A1 in fibrosis, and presents future research interests and directions in fibrotic diseases.

Cystathionine-ß-synthase is essential for AKT-induced senescence and suppresses the development of gastric cancers with PI3K/AKT activation.

Hyperactivation of oncogenic pathways downstream of RAS and PI3K/AKT in normal cells induces a senescence-like phenotype that acts as a tumor-suppressive mechanism that must be overcome during transformation. We previously demonstrated that AKT-induced senescence (AIS) is associated with profound transcriptional and metabolic changes. Here, we demonstrate that human fibroblasts undergoing AIS display upregulated cystathionine-ß-synthase (CBS) expression and enhanced uptake of exogenous cysteine, which lead to increased hydrogen sulfide (H2S) and glutathione (GSH) production, consequently protecting senescent cells from oxidative stress-induced cell death. CBS depletion allows AIS cells to escape senescence and re-enter the cell cycle, indicating the importance of CBS activity in maintaining AIS. Mechanistically, we show this restoration of proliferation is mediated through suppressing mitochondrial respiration and reactive oxygen species (ROS) production by reducing mitochondrial localized CBS while retaining antioxidant capacity of transsulfuration pathway. These findings implicate a potential tumor-suppressive role for CBS in cells with aberrant PI3K/AKT pathway activation. Consistent with this concept, in human gastric cancer cells with activated PI3K/AKT signaling, we demonstrate that CBS expression is suppressed due to promoter hypermethylation. CBS loss cooperates with activated PI3K/AKT signaling in promoting anchorage-independent growth of gastric epithelial cells, while CBS restoration suppresses the growth of gastric tumors in vivo. Taken together, we find that CBS is a novel regulator of AIS and a potential tumor suppressor in PI3K/AKT-driven gastric cancers, providing a new exploitable metabolic vulnerability in these cancers.

Differences of Corneal Biomechanics Among Thin Normal Cornea, Forme-Fruste Keratoconus, and Cornea After SMILE.

Background: To compare the corneal biomechanics of thin normal cornea (TNC) with thinnest corneal thickness (TCT) (≤500 µm), forme-fruste keratoconus (FFKC) and cornea after small incision lenticule extraction (Post-SMILE) had their central corneal thickness (CCT) matched by Corneal Visualization Scheimpflug Technology (Corvis ST). Methods: CCT were matched in 23 eyes with FFKC, 23 eyes by SMILE in 3 months post-operatively, and 23 TNC eyes. The differences in corneal biomechanics by Corvis ST among the three groups were compared. Results: There was no significant difference in CCT among the three groups, and the biomechanically corrected intraocular pressure (bIOP) did not differ significantly among the three groups (all p > 0.05). There were significant differences in most DCR parameters between pre- and post-operatively (all p < 0.05). Compared with TNC, the values of corneal deflection amplitude during the first applanation (A1DA), length at the first applanation (A1L), corneal deflection amplitude during the second applanation (A2DA), and maximum deformation amplitude (DA) decreased in 3 months after SMILE (all p < 0.05), these values increased in the FFKC (all p < 0.05). Conclusion: The majority of the DCR parameters were different among the three groups. The parameters A1DA, A1L, A2DA, and DA may be different between TNC and Post-SMILE, TNC and FFKC, and Post-SMILE and FFKC.

Therapeutic peptides: current applications and future directions.

Peptide drug development has made great progress in the last decade thanks to new production, modification, and analytic technologies. Peptides have been produced and modified using both chemical and biological methods, together with novel design and delivery strategies, which have helped to overcome the inherent drawbacks of peptides and have allowed the continued advancement of this field. A wide variety of natural and modified peptides have been obtained and studied, covering multiple therapeutic areas. This review summarizes the efforts and achievements in peptide drug discovery, production, and modification, and their current applications. We also discuss the value and challenges associated with future developments in therapeutic peptides.

Exploring the Biomechanical Properties of the Human Cornea In Vivo Based on Corvis ST.

Purpose: The aim of this study was to provide a method to determine corneal nonlinear viscoelastic properties based on the output data of corneal visualization Scheimpflug technology (Corvis ST). Methods: The Corvis ST data from 18 eyes of 12 healthy humans were collected. Based on the air-puff pressure and the corneal displacement from the Corvis ST test of normal human eyes, the work done by the air-puff attaining the whole corneal displacement was obtained. By applying a visco-hyperelastic strain energy density function of the cornea, in which the first-order Prony relaxation function and the first-order Ogden strain energy were employed, the corneal strain energy during the Corvis ST test was calculated. Then the work done by the air-puff attaining the whole corneal displacement was completely regarded as the strain energy of the cornea. The identification of the nonlinear viscoelastic parameters was carried out by optimizing the sum of difference squares of the work and the strain energy using the genetic algorithm. Results: The visco-hyperelastic model gave a good fit to the data of corneal strain energy with time during the Corvis ST test (R 2 > 0.95). The determined Ogden model parameter µ ranged from 0.42 to 0.74 MPa, and α ranged from 32.76 to 55.63. The parameters A and τ in the first-order Prony function were 0.09-0.36 and 1.21-1.95 ms, respectively. Conclusion: It is feasible to determine the corneal nonlinear viscoelastic properties based on the corneal contour information and air-puff pressure of the Corvis ST test.

A Novel Mechanism of Endoplasmic Reticulum Stress- and c-Myc-Degradation-Mediated Therapeutic Benefits of Antineurokinin-1 Receptor Drugs in Colorectal Cancer.

The neurokinin-1 receptor (NK-1R) antagonists are approved as treatment for chemotherapy-associated nausea and vomiting in cancer patients. The emerging role of the substance P-NK-1R system in oncogenesis raises the possibility of repurposing well-tolerated NK-1R antagonists for cancer treatment. This study reports that human colorectal cancer (CRC) patients with high NK-1R expression have poor survival, and NK-1R antagonists SR140333 and aprepitant induce apoptotic cell death in CRC cells and inhibit CRC xenograft growth. This cytotoxicity induced by treatment with NK-1R antagonists is mediated by induction of endoplasmic reticulum (ER) stress. ER stress triggers calcium release, resulting in the suppression of prosurvival extracellular signal-regulated kinase (ERK)-c-Myc signaling. Along with ER calcium release, one ER stress pathway mediated by protein kinase RNA-like ER kinase (PERK) is specifically activated, leading to increased expression of proapoptotic C/EBP-homologous protein (CHOP). Moreover, NK-1R antagonists enhance the efficacy of chemotherapy by increasing the sensitivity and overcoming resistance to 5-fluorouracil in CRC cells through the induction of sustained ER stress and the consequent suppression of ERK-c-Myc signaling both in vitro and in vivo. Collectively, the findings provide novel mechanistic insights into the efficacy of NK-1R antagonists either as a single agent or in combination with chemotherapy for cancer treatment.

Antimicrobial peptides: mechanism of action, activity and clinical potential.

The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria. As an excellent candidate to overcome antibiotic resistance, antimicrobial peptides (AMPs) that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity. These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action. This comprehensive review provides a broad overview of AMPs from the origin, structural characteristics, mechanisms of action, biological activities to clinical applications. We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.

Comparison of correcting myopia and astigmatism with SMILE or FS-LASIK and postoperative higher-order aberrations.

AIM: To compare the effect of myopia and astigmatism correction and postoperative change in higher-order aberration as results of receiving small-incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK). METHODS: A prospective and non-randomized controlled study was conducted. The subjects are divided into two groups according to different operations received: 229 eyes of 116 patients in the SMILE group and 168 eyes of 86 patients in the FS-LASIK group. All subjects were followed up for 3mo by monitoring their uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), spherical equivalent, higher-order aberrations, and the preoperative and postoperative complications. RESULTS: At 1wk, 1, and 3mo post-surgery, 224 eyes (97.8%), 227 eyes (99.1%) and 229 eyes (100%) had UCVA≥20/20 in the SMILE group, while 165 eyes (98.2%), 167 eyes (99.4%) and 167 eyes (99.4%) had UCVA≥20/20 in the FS-LASIK group, respectively (χ 2=0.146, 2.135, and 1.124; all P>0.05). BCVA reduction was not observed in both groups at 1 and 3mo of post-surgery (χ 2=0.734 and 1.898, P>0.05). There was no statistically significant difference in the spherical equivalent between the two groups at 1 and 3mo post-surgery, though the percentage of the spherical equivalent within ±0.50 D at 3mo post-surgery was 98% in the SMILE group, which was higher than that of the FS-LASIK group (92%, χ 2=1.872, P>0.05). The root mean square (RMS) values of total high-order aberration, coma, and spherical aberration of the two groups increased significantly in the early postoperative period and decreased after 3mo, but the values were still higher than the preoperative levels (P<0.05); there was no significant difference between the two groups in the RMS values of total higher-order aberrations and specific higher-order aberrations (P>0.05). The incidence of complications in the SMILE group was lower than that in the FS-LASIK group (χ 2=14.52, P<0.05). CONCLUSION: SMILE and FS-LASIK can effectively treat myopia, significantly improve visual acuity, and increase the total high-order aberration, spherical aberration, and coma. The incidence of complications after SMILE is relatively low.

Dorsal Pigmentation and Its Association with Functional Variation in MC1R in a Lizard from Different Elevations on the Qinghai-Tibetan Plateau.

Identification of the role of the MC1R gene has provided major insights into variation in skin pigmentation in several organisms, including humans, but the evolutionary genetics of this variation is less well established. Variation in this gene and its relationship with degree of melanism was analyzed in one of the world's highest-elevation lizards, Phrynocephalus theobaldi from the Qinghai-Tibetan Plateau. Individuals from the low-elevation group were shown to have darker dorsal pigmentation than individuals from a high-elevation group. The existence of climatic variation across these elevations was quantified, with lower elevations exhibiting higher air pressure, temperatures, and humidity, but less wind and insolation. Analysis of the MC1R gene in 214 individuals revealed amino acid differences at five sites between intraspecific sister lineages from different elevations, with two sites showing distinct fixed residues at low elevations. Three of the four single-nucleotide polymorphisms that underpinned these amino acid differences were highly significant outliers, relative to the generalized MC1R population structuring, suggestive of selection. Transfection of cells with an MC1R allele from a lighter high-elevation population caused a 43% reduction in agonist-induced cyclic AMP accumulation, and hence lowered melanin synthesis, relative to transfection with an allele from a darker low-elevation population. The high-elevation allele led to less efficient integration of the MC1R protein into melanocyte membranes. Our study identifies variation in the degree of melanism that can be explained by four or fewer MC1R substitutions. We establish a functional link between these substitutions and melanin synthesis and demonstrate elevation-associated shifts in their frequencies.