Lower Blepharoplasty with Mid-Face Elevation: A Polydioxanone (PDO) Barbed Suture Loop for Lid-Cheek Junction Blending.

BACKGROUND: Anti-aging in the lower eyelid-cheek junction area has always been the most widely sought cosmetic surgery. However, orbital fat removal or a midcheek fat pad lift alone does not achieve the best results. This study describes a new technique of lower blepharoplasty combined with a midcheek lift performed using a polydioxanone barbed suture loop based on the entire anatomy of the lower eyelid-cheek junction area. METHODS: We report our experience with lower blepharoplasty combined with a midcheek lift, covering 38 procedures performed over the past 3 years. We reviewed the technique and results and described the various indications for which the new technique is suitable. The efficacy of the surgeries was delineated using both 3D volume calculation and graphic pictures. RESULTS: All patients demonstrated significant rejuvenation of the lower eyelid with the elimination of the eyebags, elevation of the lid-cheek junction, and improvement of the nasolabial folds. All the patients were satisfied with the procedure. Complication rates were low, and lower lid retraction temporarily occurred in 3% of patients. CONCLUSIONS: This new method of lower blepharoplasty with midcheek elevation is safe, effective, convenient, and long-lasting. The technique is more doctor-friendly, recovery is quick, and complications are minimized. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Treatment of lung cancer by acupuncture combined with medicine based on pathophysiological mechanism: A review.

Lung cancer is one of the most frequently diagnosed cancers in the world. There are an estimated 2.2 million new cases and 1.79 million deaths each year. Over the past 2 decades, our understanding of disease biology, the use of predictive biomarkers, and improvements in therapeutic approaches have made significant progress and transformed the outcomes of many patients. Treatment is determined by the subtype and stage of the cancer; however, the effect of personalized treatment remains unsatisfactory. The use of Chinese medicines has attracted increasing attention worldwide. Chinese medicine treatment of lung cancer has few side effects, which can effectively prolong the survival expectation of patients and improve their quality of life, and has attracted increasing attention. Based on the pathophysiological mechanism of lung cancer reported in modern medical research, this article explores the efficacy and safety of acupuncture combined with medicine in the treatment of lung cancer.

Hydrogel-mediated extracellular vesicles for enhanced wound healing: the latest progress, and their prospects for 3D bioprinting.

Extracellular vesicles have shown promising tissue recovery-promoting effects, making them increasingly sought-after for their therapeutic potential in wound treatment. However, traditional extracellular vesicle applications suffer from limitations such as rapid degradation and short maintenance during wound administration. To address these challenges, a growing body of research highlights the role of hydrogels as effective carriers for sustained extracellular vesicle release, thereby facilitating wound healing. The combination of extracellular vesicles with hydrogels and the development of 3D bioprinting create composite hydrogel systems boasting excellent mechanical properties and biological activity, presenting a novel approach to wound healing and skin dressing. This comprehensive review explores the remarkable mechanical properties of hydrogels, specifically suited for loading extracellular vesicles. We delve into the diverse sources of extracellular vesicles and hydrogels, analyzing their integration within composite hydrogel formulations for wound treatment. Different composite methods as well as 3D bioprinting, adapted to varying conditions and construction strategies, are examined for their roles in promoting wound healing. The results highlight the potential of extracellular vesicle-laden hydrogels as advanced therapeutic tools in the field of wound treatment, offering both mechanical support and bioactive functions. By providing an in-depth examination of the various roles that these composite hydrogels can play in wound healing, this review sheds light on the promising directions for further research and development. Finally, we address the challenges associated with the application of composite hydrogels, along with emerging trends of 3D bioprinting in this domain. The discussion covers issues such as scalability, regulatory considerations, and the translation of this technology into practical clinical settings. In conclusion, this review underlines the significant contributions of hydrogel-mediated extracellular vesicle therapy to the field of 3D bioprinting and wound healing and tissue regeneration. It serves as a valuable resource for researchers and practitioners alike, fostering a deeper understanding of the potential benefits, applications, and challenges involved in utilizing composite hydrogels for wound treatment.

Ultrasound-Driven Healing: Unleashing the Potential of Chondrocyte-Derived Extracellular Vesicles for Chondrogenesis in Adipose-Derived Stem Cells.

Repairing cartilage defects represents a significant clinical challenge. While adipose-derived stem cell (ADSC)-based strategies hold promise for cartilage regeneration, their inherent chondrogenic potential is limited. Extracellular vesicles (EVs) derived from chondrocytes (CC-EVs) have shown potential in enhancing chondrogenesis, but their role in promoting chondrogenic differentiation of ADSCs remains poorly understood. Moreover, the clinical application of EVs faces limitations due to insufficient quantities for in vivo use, necessitating the development of effective methods for extracting significant amounts of CC-EVs. Our previous study demonstrated that low-intensity ultrasound (LIUS) stimulation enhances EV secretion from mesenchymal stem cells. Here, we identified a specific LIUS parameter for chondrocytes that increased EV secretion by 16-fold. CC-EVs were found to enhance cell activity, proliferation, migration, and 21-day chondrogenic differentiation of ADSCs in vitro, while EVs secreted by chondrocytes following LIUS stimulation (US-CC-EVs) exhibited superior efficacy. miRNA-seq revealed that US-CC-EVs were enriched in cartilage-regeneration-related miRNAs, contributing to chondrogenesis in various biological processes. In conclusion, we found that CC-EVs can enhance the chondrogenesis of ADSCs in vitro. In addition, our study introduces ultrasound-driven healing as an innovative method to enhance the quantity and quality of CC-EVs, meeting clinical demand and addressing the limited chondrogenic potential of ADSCs. The ultrasound-driven healing unleashes the potential of CC-EVs for chondrogenesis possibly through the enrichment of cartilage-regeneration-associated miRNAs in EVs, suggesting their potential role in cartilage reconstruction. These findings hold promise for advancing cartilage regeneration strategies and may pave the way for novel therapeutic interventions in regenerative medicine.

Diselenide Covalent Allosteric Inhibitors of Glutaminase with Strong In Vivo Anticancer Activity.

Allosteric glutaminase inhibitors demonstrate inhibition of glutamine-dependent cancer cells with low general drug toxicity, but have issues with efficacy in vivo. Here, we designed a series of diselenide compounds with 6 atoms in the middle, aiming to target the allosteric site of kidney type glutaminase (KGA) with a covalent linkage to strengthen the interaction. Proteomic analysis demonstrated that the diselenide compounds cross-linked with the Lys320 residue at the KGA allosteric site; this was confirmed by the KGA K320A mutant which showed essentially no binding to the diselenide. Further, structure-activity relationship (SAR) analysis demonstrated that growth inhibition correlated well with KGA inhibition and was enhanced by thioredoxin reductase (TrxR) inhibition. Interestingly, diselenide compounds showed no inhibition of glutamate dehydrogenase (GDH), indicating some enzyme selectivity. Importantly, the designed novel diselenides are glutaminase allosteric inhibitors that showed in vivo efficacy and survival in the xenograft animal model.

Glutamate dehydrogenase: Potential therapeutic targets for neurodegenerative disease.

Glutamate dehydrogenase (GDH) is a key enzyme in mammalian glutamate metabolism. It is located at the intersection of multiple metabolic pathways and participates in a variety of cellular activities. GDH activity is strictly regulated by a variety of allosteric compounds. Here, we review the unique distribution and expressions of GDH in the brain nervous system. GDH plays an essential role in the glutamate-glutamine-GABA cycle between astrocytes and neurons. The dysfunction of GDH may induce the occurrence of many neurodegenerative diseases, such as Parkinson's disease, epilepsy, Alzheimer's disease, schizophrenia, and frontotemporal dementia. GDH activators and gene therapy have been found to protect neurons and improve motor disorders in neurodegenerative diseases caused by glutamate metabolism disorders. To date, no medicine has been discovered that specifically targets neurodegenerative diseases, although several potential medicines are used clinically. Targeting GDH to treat neurodegenerative diseases is expected to provide new insights and treatment strategies.

Preparation of therapy-grade extracellular vesicles from adipose tissue to promote diabetic wound healing.

Background: Treatment of diabetic wounds is a major challenge in clinical practice. Extracellular vesicles (EVs) from adipose-derived stem cells have shown effectiveness in diabetic wound models. However, obtaining ADSC-EVs requires culturing vast numbers of cells, which is hampered by the need for expensive equipment and reagents, extended time cost, and complicated procedures before commercialization. Therefore, methods to extract EVs from discarded tissue need to be developed, for immediate application during surgery. For this reason, mechanical, collagenase-digestive, and constant in-vitro-collective methods were designed and compared for preparing therapy-grade EVs directly from adipose tissue. Methods: Characteristics and quantities of EVs were detected by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting firstly. To investigate the biological effects of EVs on diabetic wound healing, angiogenesis, proliferation, migration, and inflammation-regulation assays were then evaluated in vitro, along with a diabetic wound healing mouse model in vivo. To further explore the potential therapeutic mechanism of EVs, miRNA expression profile of EVs were also identified and analyzed. Results: The adipose tissue derived EVs (AT-EVs) were showed to qualify ISEV identification by nanoparticle tracking analysis and Western blotting and the AT-EVs yield from three methods was equal. EVs also showed promoting effects on biological processes related to diabetic wound healing, which depend on fibroblasts, keratinocytes, endothelial cells, and macrophages both in vitro and in vivo. We also observed enrichment of overlapping or unique miRNAs originate from different types of AT-EVs associated with diabetic wound healing for further investigation. Conclusion: After comparative analyses, a mechanical method was proposed for preparing immediate clinical applicable EVs from adipose tissue that would result in reduced preparation time and lower cost, which could have promising application potential in treating diabetic wounds.

Synthesis of Novel Kidney-Type Glutaminase Allosteric Inhibitors Targeting the Critical Lys-320 Residue.

Reversible allosteric inhibitors of kidney-type glutaminase (GLS1, KGA) showed incomplete inhibition of cancer cell proliferation and poor in vivo efficacy. Here, we investigate some irreversible inhibitors targeting the critical K320 residue responsible for GLS1 biological activity. The (trifluoromethoxy)phenylacetic acid motif was replaced by α,ß-unsaturated carboxylic acids, and the resulting terminally substituted CB839 derivatives (e.g., GJ2 and GJ5) showed good stability in solid form at room temperature, and better liver microsome stability and in vivo pharmacokinetics than coumarin. Both compounds showed binding to the wild-type KGA, whose K D is 106-fold stronger than that of CB839, but only weak binding to the KGA K320A mutant and no inhibition of GDH proteins. Interestingly, GJ2 treatment significantly decreased the trypsin digestion of KGA, tumor cell clonal formation, and cancer cell growth rate. Taking these results together, targeting the critical K320 residue of GLS1 might be a new strategy to make a potent GLS1 allosteric inhibitor.

Production and Biological Effects of Extracellular Vesicles from Adipose-Derived Stem Cells Were Markedly Increased by Low-Intensity Ultrasound Stimulation for Promoting Diabetic Wound Healing.

Diabetic wound treatment has posed a significant challenge in clinical practice. As a kind of cell-derived nanoparticles, extracellular vesicles produced by adipose-derived stem cells (ADSC-EVs) have been reported to be potential agents for diabetic wound treatment. However, ADSC-EV yield is insufficient to meet the demands of clinical therapy. In this study, a novel method involving the use of low-intensity ultrasound stimulation on ADSCs is developed to promote EV secretion for clinical use. A proper low-intensity ultrasound stimulation parameter which significantly increases ADSC-EV quantity has been found. In addition, EVs secreted by ADSCs following low-intensity ultrasound stimulation (US-EVs) are enriched in wound healing-related miRNAs. Moreover, US-EVs promote the biological functions of fibroblasts, keratinocytes, and endothelial cells in vitro, and promote diabetic wound healing in db/db mice in vivo through re-epithelialization, collagen production, cell proliferation, keratinocyte differentiation and migration, and angiogenesis. This study proposes low-intensity ultrasound stimulation as a new method for promoting significant EV secretion by ADSCs and for improving the diabetic wound-healing potential of EVs, which will meet the clinical needs for these nanoparticles. The production of extracellular vesicles of adipose-derived stem cells is obviously promoted by a low-intensity ultrasound stimulation method, and the biological effects of promoting diabetic wound healing were markedly increased in vitro and in vivo.

Studies in the antiviral molecular mechanisms of 25-hydroxycholesterol: Disturbing cholesterol homeostasis and post-translational modification of proteins.

Efficient antiviral drug discovery has been a pressing issue of global public health concern since the outbreak of coronavirus disease 2019. In recent years, numerous in vitro and in vivo studies have shown that 25-hydroxycholesterol (25HC), a reactive oxysterol catalyzed by cholesterol-25-hydroxylase, exerts broad-spectrum antiviral activity with high efficiency and low toxicity. 25HC restricts viral internalization and disturbs the maturity of viral proteins using multiple mechanisms. First, 25HC reduces lipid rafts and cholesterol in the cytomembrane by inhibiting sterol-regulatory element binding proteins-2, stimulating liver X receptor, and activating Acyl-coenzyme A: cholesterol acyl-transferase. Second, 25HC impairs endosomal pathways by restricting the function of oxysterol-binding protein or Niemann-pick protein C1, causing the virus to fail to release nucleic acid. Third, 25HC disturbs the prenylation of viral proteins by suppressing the sterol-regulatory element binding protein pathway and glycosylation by increasing the sensitivity of glycans to endoglycosidase. This paper reviews previous studies on the antiviral activity of 25HC in order to fully understand its role in innate immunity and how it may contribute to the development of urgently needed broad-spectrum antiviral drugs.

Stabilization of zein nanoparticles with k-carrageenan and tween 80 for encapsulation of curcumin.

We aimed to develop a stable nanosystem with k-carrageenan (Kc), an anionic polysaccharide, combined with tween 80 to stabilize zein nanoparticles. The experimental results showed that the particle size, zeta-potential, and stability of the system depend on the Kc amount when the zein amount was unchanged. We found that the nanosystem with 5.0 and 10.0 mg Kc had a smaller particle size (250.1 ± 0.9 and 287.6 ± 1.4 nm, respectively), low polydispersity index (PDI, ≤ 0.20), and high stability when the external conditions changed. No obvious flocculation or deposition was observed at pH of 3-9, salt ion concentrations of 0-500 mmol/L, temperature of 30 °C and 50 °C-90 °C, and storage at 4 °C for 30 days. When the Kc-ZNP system was loaded with curcumin (Cur), there was a good encapsulation effect (5.0 mg Kc with 1.00 mg Cur (EE (%) = 34.69% ± 2.02%, size = 380.23 ± 5.80 nm, PDI = 0.252 ± 0.018) and 10.0 mg Kc with 2.00 mg Cur (EE (%) = 20.13% ± 1.05%, size = 431.27 ± 0.78 nm, PDI = 0.269 ± 0.020), ensuring that the particle size was not too large. Therefore, Kc-ZNPs could be a potential delivery system for fat-soluble drugs.

Fabrication of Ion-Crosslinking Aminochitosan Nanoparticles for Encapsulation and Slow Release of Curcumin.

Curcumin (Cur) has anticancer activities but has poor stability, which can be improved using carrier materials. In this study, chitosan was aminated to increase the number of amino groups on its surface, modified with folic acid (FA), and then made into nanoparticles by ionic crosslinking. Owing to ion interaction, the negatively charged, non-toxic tripolyphosphate (TPP) interacted with the positively charged amino group on the aminated chitosan (AmCS) surface, producing FA-AmCS-TPP nanoparticles, which were then characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectrophotometry (FT-IR), and thermogravimetric analysis (TGA). Their small particle size (175.2 ± 0.99 nm) and good surface positive potential (+42.4 mV) are beneficial for carrying antitumor drugs. We subsequently investigated whether coating of Cur by AmCS allows slow drug release by FA-AmCS-TPP nanoparticles in different pH environments, and estimated the Cur loading efficiency (EE-Cur). Our results showed that the cumulative release rate of Cur at 48 h was 56.2%, and that the EE-Cur reached 94.26 ± 0.91% with nanoparticles composed of 0.10 g AmCS, 10.0 mg FA, 10.0 mg TPP, and 15.0 mg Cur. Additionally, cytotoxicity experiments showed that the Cur/FA-AmCS-TPP nanoparticles had good targeting ability for tumor cells. Therefore, the non-toxic targeted composite nanoparticles had potential as a new antitumor agent that can overcome the limitations of Cur.