Endoplasmic reticulum stress involved in high-fat diet and palmitic acid-induced vascular damages and fenofibrate intervention.

Fenofibrate (FF) is widely used to lower blood lipids in clinical practice, but whether its protective effect on endothelium-dependent vasodilatation (EDV) in thoracic aorta is related with endoplasmic reticulum (ER) stress remains unknown. In this study, female Sprauge Dawley rats were divided into standard chow diets (SCD), high-fat diets (HFD) and HFD plus FF treatment group (HFD + FF) randomly. The rats of latter two groups were given HFD feeding for 5 months, then HFD + FF rats were treated with FF (30 mg/kg, once daily) via gavage for another 2 months. The pathological and tensional changes, protein expression of eNOS, and ER stress related genes in thoracic aorta were measured. Then impacts of palmitic acid (PA) and FF on EDV of thoracic aorta from normal female SD rats were observed. Ultimately the expression of ER stress related genes were assessed in primary mouse aortic endothelial cells (MAEC) treated by fenofibric acid (FA) and PA. We found that FF treatment improved serum lipid levels and pathological changes in thoracic aorta, accompanied with decreased ER stress and increased phosphorylation of eNOS. FF pretreatment also improved EDV impaired by different concentrations of PA treatment. The dose- and time-dependent inhibition of cell proliferation by PA were inverted by FA pretreatment. Phosphorylation of eNOS and expression of ER stress related genes were all inverted by FA pretreatment in PA-treated MAEC. Our findings show that fenofibrate recovers damaged EDV by chronic HFD feeding and acute stimulation of PA, this effect is related with decreased ER stress and increased phosphorylation of eNOS.

Enhancing diabetic wound healing: advances in electrospun scaffolds from pathogenesis to therapeutic applications.

Diabetic wounds are a significant subset of chronic wounds characterized by elevated levels of inflammatory cytokines, matrix metalloproteinases (MMPs), and reactive oxygen species (ROS). They are also associated with impaired angiogenesis, persistent infection, and a high likelihood of hospitalization, leading to a substantial economic burden for patients. In severe cases, amputation or even mortality may occur. Diabetic foot ulcers (DFUs) are a common complication of diabetes, with up to 25% of diabetic patients being at risk of developing foot ulcers over their lifetime, and more than 70% ultimately requiring amputation. Electrospun scaffolds exhibit a structural similarity to the extracellular matrix (ECM), promoting the adhesion, growth, and migration of fibroblasts, thereby facilitating the formation of new skin tissue at the wound site. The composition and size of electrospun scaffolds can be easily adjusted, enabling controlled drug release through fiber structure modifications. The porous nature of these scaffolds facilitates gas exchange and the absorption of wound exudate. Furthermore, the fiber surface can be readily modified to impart specific functionalities, making electrospinning nanofiber scaffolds highly promising for the treatment of diabetic wounds. This article provides a concise overview of the healing process in normal wounds and the pathological mechanisms underlying diabetic wounds, including complications such as diabetic foot ulcers. It also explores the advantages of electrospinning nanofiber scaffolds in diabetic wound treatment. Additionally, it summarizes findings from various studies on the use of different types of nanofiber scaffolds for diabetic wounds and reviews methods of drug loading onto nanofiber scaffolds. These advancements broaden the horizon for effectively treating diabetic wounds.

Application and Development of Electrospun Nanofiber Scaffolds for Bone Tissue Engineering.

Nanofiber scaffolds have gained significant attention in the field of bone tissue engineering. Electrospinning, a straightforward and efficient technique for producing nanofibers, has been extensively researched. When used in bone tissue engineering scaffolds, electrospun nanofibers with suitable surface properties promote new bone tissue growth and enhance cell adhesion. Recent advancements in electrospinning technology have provided innovative approaches for scaffold fabrication in bone tissue engineering. This review comprehensively examines the utilization of electrospun nanofibers in bone tissue engineering scaffolds and evaluates the relevant literature. The review begins by presenting the fundamental principles and methodologies of electrospinning. It then discusses various materials used in the production of electrospun nanofiber scaffolds for bone tissue engineering, including natural and synthetic polymers, as well as certain inorganic materials. The challenges associated with these materials are also described. The review focuses on novel electrospinning techniques for scaffold construction in bone tissue engineering, such as multilayer nanofibers, multifluid electrospinning, and the integration of electrospinning with other methods. Recent advancements in electrospinning technology have enabled the fabrication of precisely aligned nanofiber scaffolds with nanoscale architectures. These innovative methods also facilitate the fabrication of biomimetic structures, wherein bioactive substances can be incorporated and released in a controlled manner for drug delivery purposes. Moreover, they address issues encountered with traditional electrospun nanofibers, such as mechanical characteristics and biocompatibility. Consequently, the development and implementation of novel electrospinning technologies have revolutionized scaffold fabrication for bone tissue engineering.

Influence of Fracturing on a Coal Structure during Coalbed Methane Stimulation.

The impact of fracturing on coal seams includes not only mechanical alterations but also physical and chemical alterations. The coupling of these alterations plays an important role in the recovery of coalbed methane (CBM). 13C nuclear magnetic resonance (13C NMR), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), and molecular models were conducted on coals with different degrees of fracturing to study the alterations in the coal structure during CBM stimulation. The 13C NMR results show that some aliphatic chains and oxygen-containing functional groups were shed, and some aliphatic rings were broken due to the effects of fracturing, which cause an increase in the relative content of aromatic carbon. The HRTEM and XRD results indicate that fracturing will result in a decrease in the interlayer spacing d002, an increase in the stacking height Lc, and a slight increase in the layer size La. Moreover, the orientation distribution in fractured coal was more intensive. The construction of molecular models also verified the variation of surface functional groups and interlayer spacing. Based on these analyses and molecular models, the alteration mechanism of functional groups and aromatic structures under fracturing was demonstrated. This study clarifies the alteration of the coal structure by fracturing and has important implications for the recovery of CBM.

Preparation and Investigation of Cellulose Acetate/Gelatin Janus Nanofiber Wound Dressings Loaded with Zinc Oxide or Curcumin for Enhanced Antimicrobial Activity.

The skin, as the largest organ, serves as a protective barrier against external stimuli. However, when the skin is injured, wound healing becomes a complex process influenced by physiological conditions, bacterial infections, and inflammation. To improve the process of wound healing, a variety of wound dressings with antibacterial qualities have been created. Electrospun nanofibers have gained significant attention in wound dressing research due to their large specific surface area and unique structure. One interesting method for creating Janus-structured nanofibers is side-by-side electrospinning. This work used side-by-side electrospinning to make cellulose acetate/gelatin Janus nanofibers. Curcumin and zinc oxide nanoparticles were added to these nanofibers. We studied Janus nanofibers' physicochemical characteristics and abilities to regulate small-molecule medication release. Janus nanofibers coated with zinc oxide nanoparticles and curcumin were also tested for antibacterial activity. The Janus nanofibers with specified physicochemical characteristics were successfully fabricated. Nanofibers released small-molecule medicines in a controlled manner. Additionally, the Janus nanofibers loaded with curcumin exhibited excellent antibacterial capabilities. This research contributes to the development of advanced wound dressings for promoting wound healing and combating bacterial infections.

Advances in the Preparation of Nanofiber Dressings by Electrospinning for Promoting Diabetic Wound Healing.

Chronic diabetic wounds are one of the main complications of diabetes, manifested by persistent inflammation, decreased epithelialization motility, and impaired wound healing. This will not only lead to the repeated hospitalization of patients, but also bear expensive hospitalization costs. In severe cases, it can lead to amputation, sepsis or death. Electrospun nanofibers membranes have the characteristics of high porosity, high specific surface area, and easy functionalization of structure, so they can be used as a safe and effective platform in the treatment of diabetic wounds and have great application potential. This article briefly reviewed the pathogenesis of chronic diabetic wounds and the types of dressings commonly used, and then reviewed the development of electrospinning technology in recent years and the advantages of electrospun nanofibers in the treatment of diabetic wounds. Finally, the reports of different types of nanofiber dressings on diabetic wounds are summarized, and the method of using multi-drug combination therapy in diabetic wounds is emphasized, which provides new ideas for the effective treatment of diabetic wounds.

LncRNA POU3F3 promotes melanoma cell proliferation by downregulating lncRNA MEG3.

BACKGROUND: LncRNA POU3F3 (POU3F3) is overexpressed and plays oncogenic roles in esophageal squamous-cell carcinomas. LncRNA MEG3 (MEG3) has been characterized as a tumor suppressive lncRNA in different types of cancer. Our preliminary deep sequencing analysis revealed the inverse correlation between POU3F3 and MEG2 across melanoma tissues, indicating the interaction between them in melanoma. Therefore, this study was performed to investigate the crosstalk between POU3F3 and MEG3 in melanoma. METHODS: Tumor and adjacent healthy tissues collected from 60 melanoma patients were subjected to RNA extractions and RT-qPCRs to analyze the differential expression of POU3F3 and MEG2 in melanoma. In melanoma cells, POU3F3 and MEG2 were overexpressed to study the interactions between them. CCK-8 assays were performed to analyze the roles of POU3F3 and MEG2 in regulating melanoma cell proliferation. RESULTS: We found that POU3F3 was upregulated, while lncRNA MEG3 was downregulated in melanoma. Expression levels of POU3F3 and MEG3 were inversely correlated across tumor tissues. In vitro experiments showed that POU3F3 overexpression decreased MEG3 expression in melanoma cells, while MEG3 overexpression failed to affect POU3F3. POU3F3 overexpression increased melanoma cell proliferation, while MEG3 overexpression decreased melanoma cell proliferation. In addition, rescue experiments showed that MEG3 overexpression attenuated the enhancing effects of POU3F3 overexpression. CONCLUSION: POU3F3 may promote melanoma cell proliferation by downregulating MEG3.

Inhibitory effect of 17ß­estradiol on triglyceride synthesis in skeletal muscle cells is dependent on ESR1 and not ESR2.

The present study aimed to investigate the inhibitory effects and the mechanisms underlying 17ß­estradiol (E2) effects on triglyceride synthesis and insulin resistance in skeletal muscle tissues and cells. Ovariectomy (OVX) was performed on 6­month­old female rats treated with or without E2. Subsequently, various serum biochemical markers were measured. Additionally, pathological alterations of the uterus, liver and skeletal muscle were analyzed, and the content of triglycerides (TG) in muscle was detected. Differentiated myotubes formed by C2C12 cells were treated with palmitic acid (PA) or pretreated with E2, estrogen receptor (ESR) 1 agonist propylpyrazoletriol (PPT) and ESR2 agonist diarylpropionitrile (DPN). Subsequently, the mRNA or protein expression levels of ESR1/2, peroxisome proliferator activated receptor α (PPARα), CD36 molecule (CD36), fatty acid synthase (FASN), perilipin 2 (PLIN2), phosphorylated acetyl­CoA carboxylase α (p­ACACA), p­AKT serine/threonine kinase (p­AKT) and p­mitogen­activated protein kinase 8 (p­MAPK8) were analyzed in skeletal muscle or in C2C12 cells by reverse transcription­semi­quantitative polymerase chain reaction and western blotting. The present results suggested that treatment with E2 inhibited OVX­induced body weight gain, TG accumulation and insulin resistance. The protein or mRNA expression levels of ESR1, CD36, PPARα, p­ACACA and p­AKT were decreased, whereas the protein or mRNA expression levels of ESR2, PLIN2, FASN and p­MAPK8 were increased in the OVX group. Of note, treatment with E2 restored the expression levels of the aforementioned factors. In C2C12 cells, treatment with E2 or PPT reversed the alterations induced by treatment with PA. In contrast, pretreatment with DPN did not influence the effect of PA. Collectively, E2 was able to interact with ESR1, thus activating the CD36­PPARα pathway, decreasing the level of TG in the muscles and improving insulin resistance in skeletal muscles and C2C12 cells.

Effects of a standard high-fat diet with or without multiple deficiencies on bone parameters in ovariectomized mature rat.

The aim of this study was to determine the effects of a standard high fat diet (D12451) with or without vitamin D3, phosphorus, and calcium (i.e., high-fat diet [HFD] or high-fat deficient diet [HFDD]) on the bone parameters of ovariectomized female rats. Six-month-old of female Sprauge Dawley (SD) rats were randomly divided into six study groups: sham operation with standard chow diet (SSCD), sham operation with a HFD (SHFD), sham operation with a HFDD (SHFDD), ovariectomized (OVX), OVX with a HFD (OVX-HFD), and OVX with a HFDD (OVX-HFDD). A bilateral ovariectomy was administered to the OVX, OVX-HFD, and OVX-HFDD rats, while the SSCD, SHFD, and SHFDD rats were only given a laparotomy. Multiple analyses concerning the glucose and insulin tolerance, structure, bone strength, bone matrix, and mineralization of the rats were conducted in order to produce a detailed characterization of the effects of a HFD and a HFDD on postmenopausal osteoporotic rats. Seven months of HFD and HFDD feeding resulted in obesity and insulin resistance in female SD rats. A standard HFD increased the bone calcium content and bone strength of OVX rats. Conversely, the serum N-mid osteocalcin (N-MID-OT) and tartrate-resistant acid phosphatase (TRAP) levels in the OVX-HFDD group were increased, accompanied by a clear decrease in the bone mineral density (BMD), bone mineral content (BMC), bone calcium and bone strength, as well as reduced osteocalcin expression. A HFDD weakened the activity of the osteoblasts while aggravating bone loss and decreasing bone strength in ovariectomized rats, which may be due to the calcium, phosphorus and vitamin D3 deficiencies in the diet.

Topical Application of Insulin Accelerates Vessel Maturation of Wounds by Regulating Angiopoietin-1 in Diabetic Mice.

Reestablishment of the structural and functional microvasculature would be beneficial to promote healing of diabetic wounds. We explored the role of insulin application on microvascular maturation of diabetic wounds to determine whether it is associated with insulin-induced wound healing. We adopted the multiple injections of streptozotocin (STZ) to establish a diabetic animal model. The effect of insulin on microvessel formation, especially the effect of insulin on microvascular maturation was observed by transmission electron microscopy and laser scanning confocal microscopy. The pivotal protein regulated by insulin during healing processes was explored by tropical application neutralizing antibodies to these proteins; the specific protein was further confirmed using immunoblotting. On days 7 and 11, the blood vessel in insulin-treated wounds was surrounded by more α-smooth muscle actin (α-SMA) expressing cells. The blockage of angiopoietin-1 (Ang-1), but not angiopoietin-2 (Ang-2) or platelet-derived growth factor-B (PDGF-B), resulted in reduced maturation of newly formed blood vessels despite the presence of insulin in vivo. Further analysis showed that insulin induced an increased expression of Ang-1. The blood vessels in insulin-treated wounds showing advanced coverage of pericytes and reconstruction of new vascular basement membrane suggest that insulin is a potent accelerator of microvascular maturation, which may be involved in the mechanisms of insulin-induced wound healing.