Optimization study on wet electrostatic powder coating process to manufacture UHMWPE/LDPE towpregs

In the present study, an attempt has been made to coat the non-conductive Ultra-high Molecular Weight Polyethylene (UHMWPE) fibers with Low-Density Polyethylene (LDPE) powder. In order to enable the deposition of electrostatically charged LDPE powder onto the fiber surface, UHMWPE fibers are dipped into a surface modification bath to impart momentary conductivity. Further, Box Behnken’s experimental design is used to optimize the processing parameters for Fiber Volume Fraction (Vf) for this wet electrostatic spray coating process. An experimental multi-parametric equation is acquired through response surface methodology to ascertain the association amid the process parameters such as processing temperature (A), conveying air pressure (B), and gun nozzle angle (C) on the output response of Vf. The process parametric values for A, B, and C are varied from 225°C to 245°C, 0.2 bar to 0.4 bar, and 0° to 120° respectively. The Vf obtained is in the range of 37.02%–56.28% depending on the combination of process parametric values. Powder pick-up increases with an increase in the gun nozzle angle. An increase in conveying air pressure and temperature of the hot air oven leads to an increase in powder deposition. The values predicted from the model are observed to be in close proximity (94.59%) to the experimental results. Gun nozzle angle is the principal parameter affecting the matrix deposition on the fiber surface in comparison to other process parameters.

The Potential Role of Cellular Senescence in Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) represents an increasing global health burden. Cellular senescence develops in response to cellular injury, leading not only to cell cycle arrest but also to alterations of the cellular phenotype and metabolic functions. In this review, we critically discuss the currently existing evidence for the involvement of cellular senescence in NAFLD in order to identify areas requiring further exploration. Hepatocyte senescence can be a central pathomechanism as it may foster intracellular fat accumulation, fibrosis and inflammation, also due to secretion of senescence-associated inflammatory mediators. However, in some non-parenchymal liver cell types, such as hepatic stellate cells, senescence may be beneficial by reducing the extracellular matrix deposition and thereby reducing fibrosis. Deciphering the detailed interaction between NAFLD and cellular senescence will be essential to discover novel therapeutic targets halting disease progression.

Circular RNAs in Intervertebral Disc Degeneration: An Updated Review

Low back pain, a common medical condition, could result in severe disability and inflict huge economical and public health burden. Its pathogenesis is attributed to multiple etiological factors, including intervertebral disc degeneration (IDD). Emerging evidence suggests that circular RNAs (circRNAs), a major type of regulatory non-coding RNA, play critical roles in cellular processes that are pertinent to IDD development, including nucleus pulposus cell proliferation and apoptosis as well as extracellular matrix deposition. Increasing number of translational studies also indicated that circRNAs could serve as novel biomarkers for the diagnosis of IDD and/or predicting its clinical outcomes. Our review aims to discuss the recent progress in the functions and mechanisms of newly discovered IDD-related circRNAs.

A highly porous type II collagen containing scaffold for the treatment of cartilage defects enhances MSC chondrogenesis and early cartilaginous matrix deposition.

A major challenge in cartilage tissue engineering (TE) is the development of instructive and biomimetic scaffolds capable of driving effective mesenchymal stem cell (MSC) chondrogenic differentiation and robust de novo...

Extracellular Vesicles in Pulmonary Fibrosis Models and Biological Fluids of Interstitial Lung Disease Patients: A Scoping Review

Introduction: Interstitial lung diseases (ILDs) are a heterogeneous group of diffuse parenchymal lung disorders characterized by the pathogenetic involvement of interstitium. Therefore, an elucidation of the etiology and pathogenesis as well as the identification of diagnostic and prognostic biomarkers of such diseases is more compelling than ever. It is of note that there is increasing evidence of the involvement of extracellular vesicles (EVs) in the pathogenesis of lung diseases including lung cancer, chronic obstructive pulmonary disease and pulmonary fibrosis. It has been speculated that EVs play a pivotal role as mediators of intercellular communication, as well as the highlighting of the role of EVs as co-operators in the development of lung diseases such as IPF. Methods: The present study aimed to carry out a systematic exploratory search of the literature (through the scoping review approach) to identify and systematize the main results of the pathogenetic role of EVs in pulmonary fibrosis models and biological fluids from ILD patients, including plasma, bronchoalveolar lavage (BAL) and sputum. Conclusion: Fibroblast-to-mesenchymal differentiation, collagen and extracellular matrix deposition are key mechanisms in the development and progression of IPF. EV-coupled miRNA are important modulators of biological processes in terms of intercellular communication as shown in pulmonary fibrosis models as well as biofluids. The helpfulness of EVs as diagnostic and theranostic markers is worth further investigation. The evolving potential of EVs to translate effective EV-based therapies into clinical practice is of growing interest, due to the urgent need for novel therapeutic strategies for IPF patients.

Immunological Regulation of Intestinal Fibrosis in Inflammatory Bowel Disease

Intestinal fibrosis is a late-stage phenotype of inflammatory bowel disease (IBD), which underlies most of the long-term complications and surgical interventions in patients, particularly those with Crohn’s disease. Despite these issues, antifibrotic therapies are still scarce, mainly due to the current lack of understanding concerning the pathogenetic mechanisms that mediate fibrogenesis in patients with chronic intestinal inflammation. In the current review, we summarize recent evidence regarding the cellular and molecular factors of innate and adaptive immunity that are considered critical for the initiation and amplification of extracellular matrix deposition and stricture formation. We focus on the role of cytokines by dissecting the pro- vs antifibrotic components of the immune response, while taking into consideration their temporal association to the progressive stages of the natural history of IBD. We critically present evidence from animal models of intestinal fibrosis and analyze inflammation-fibrosis interactions that occur under such experimental scenarios. In addition, we comment on recent findings from large-scale, single-cell profiling of fibrosis-relevant populations in IBD patients. Based on such evidence, we propose future potential targets for antifibrotic therapies to treat patients with IBD.

Jian-Pi-Yi-Shen Formula Alleviates Chronic Kidney Disease in Two Rat Models by Modulating QPRT/NAD+/SIRT3/Mitochondrial Dynamics Pathway

Objective. Jian-Pi-Yi-Shen formula (JPYSF) is a traditional Chinese herbal decoction and has been used for treating chronic kidney disease (CKD) in clinics for decades. However, the potential mechanisms have not been fully elucidated. This study was designed to test the efficacy of JPYSF in treating CKD and explore the underlying mechanism. Methods. Two CKD rat models were established by 5/6 nephrectomy (5/6 Nx) and feeding with adenine-containing feed, respectively. The intervention dose of JPYSF was 10.89 g/kg/d by gastric irrigation. Renal function was assessed by serum creatinine (Scr) and blood urea nitrogen (BUN). Periodic acid-Schiff (PAS) and Masson’s trichrome staining were used to evaluate renal histopathological changes. The levels of nicotinamide adenine dinucleotide (NAD+) were measured by using the enzyme-linked immunosorbent assay kit. The proteins expressions of renal fibrosis, quinolinate phosphoribosyltransferase (QPRT), sirtuin 3 (SIRT3), and mitochondrial dynamics were determined and quantified by Western blot analysis. Results. The results show that administration of JPYSF significantly lowered Scr and BUN levels, improved renal tubular atrophy and interstitial fibrosis, and decreased renal extracellular matrix deposition in two CKD rat models. In addition, CKD rats exhibited suppressed QPRT/NAD+/SIRT3 signal, increased mitochondrial fission, and decreased mitochondrial fusion. JPYSF treatment promoted QPRT/NAD+/SIRT3 signal and restored mitochondrial fission/fusion balance. Conclusion. In conclusion, administration of JPYSF effectively alleviated CKD progression in two rat models, which may be related with regulation of the QPRT/NAD+/SIRT3/mitochondrial dynamics pathway.

Determination of the Role of the Distal Outflow Pathway Tissue in Glucocorticoid-induced Ocular Hypertension

Introduction Prolonged application of glucocorticoids (GCs) induces ocular hypertension (OHT) and glaucoma. This increased intraocular pressure (IOP) is due to pathological changes in the trabecular meshwork (TM) outflow pathway tissues including impaired cell functions and extracellular matrix deposition. The changes and role of the TM in GC-induced OHT have been well studied. However, the role of the tissues distal to the TM (distal outflow tissues) is unclear. This study aims to further uncover the role of distal outflow tissue in GC-induced OHT using a novel perfusion organ culture (POC) model. Methods Huma corneal rims tissues were attached to 3D printed transparent perfusion plates using a combination of thin and thick glues. The artificial anterior chamber was perfused with DMEM-low glucose medium at 2ul/min to mimic aqueous humor production, and IOP was recorded using pressure transducers and a computerized system. To determine the role of distal tissue in GC-induced IOP changes, the TM tissue was carefully removed from both eyes, and one eye was treated with ethanol (EtOH) and the fellow eye with dexamethasone (DEX). Results The model was validated through a comparison of the IOP and TM stiffness of glue contaminated to non-contaminated corneal rims. The glue contaminated rim showed highly increased IOP and TM stiffness while the non-contaminated rim showed normal values. After validation, the TM was removed from paired corneal rims. One rim was treated with 100nM DEX and the fellow rim with 0.1% EtOH. The DEX treated rim showed increase in IOP while the EtOH control showed little change. Conclusion We created a novel corneal rim perfusion culture model for the study of GC-induced OHT. This model showed promising results of distal outflow involvement in glucocorticoid induced ocular hypertension. Further studies are needed to elucidate the role of distal outflow tissues in GC responsiveness in the eye.

MiR-200c-3p targets SESN1 and represses the IL-6/AKT loop to prevent cholangiocyte activation and cholestatic liver fibrosis

Cholestasis causes ductular reaction in the liver where the reactive cholangiocytes not only proliferate but also gain a neuroendocrine-like phenotype, leading to inflammatory cell infiltration and extracellular matrix deposition and contributing to the development and progression of cholestatic liver fibrosis. This study aims to elucidate the role of miR-200c in cholestasis-induced biliary liver fibrosis and cholangiocyte activation. We found that miR-200c was extremely abundant in cholangiocytes but was reduced by cholestasis in a bile duct ligation (BDL) mouse model; miR-200c was also decreased by bile acids in vitro. Phenotypically, loss of miR-200c exacerbated cholestatic liver injury, including periductular fibrosis, intrahepatic inflammation, and biliary hyperplasia in both the BDL model and the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) model. We identified sestrin 1 (SESN1) as a target of miR-200c. Sesn1−/−-BDL mice showed mitigation of cholestatic liver injury. On a molecular level, the pro-proliferative IL-6/AKT feedback loop was activated in Mir200c−/− livers but was inhibited in Sesn1−/− livers upon cholestasis in mice. Furthermore, rescuing expression of miR-200c by the adeno-associated virus serotype 8 ameliorated BDL-induced liver injury in Mir200c−/− mice. Taken together, this study demonstrates that miR-200c restrains the proliferative and neuroendocrine-like activation of cholangiocytes by targeting SESN1 and inhibiting the IL-6/AKT feedback loop to protect against cholestatic liver fibrosis. Our findings provide mechanistic insights regarding biliary liver fibrosis, which may help to reveal novel therapeutic targets for the treatment of cholestatic liver injury and liver fibrosis.

Histologically Confirmed Recellularization is a Key Factor that Affects Meniscal Healing in Immature and Mature Meniscal Tears

Healing outcomes of meniscal repair are better in younger than in older. However, exact mechanisms underlying superior healing potential in younger remain unclear from a histological perspective. This study included 24 immature rabbits and 24 mature rabbits. Tears were created in the anterior horn of medial meniscus of right knee in each rabbit. Animals were sacrificed at 1, 3, 6, and 12 weeks postoperatively. We performed macroscopic and histological evaluations of post-meniscal repair specimens. Cells were counted within a region of interest to confirm cellularization at tear site in immature menisci. The width of cell death zone was measured to determine the region of cell death in mature menisci. Apoptosis was evaluated by TUNEL assay. Vascularization was assessed by CD31 immunofluorescence. The glycosaminoglycans and the types 1 and 2 collagen content was evaluated by calculating average optical density of corresponding histological specimens. Cartilage degeneration was also evaluated. Healing outcomes following untreated meniscal tears were superior in immature group. Recellularization with meniscus-like cell morphology was observed at tear edge in immature menisci. Superior recellularization was observed at meniscal sites close to joint capsule than at sites distant from the capsule. Recellularization did not occur at tear site in mature group; however, we observed gradual enlargement of cell death zone. Apoptosis was presented at 1, 3, 6, 12 weeks in immature and mature menisci after untreated meniscal tears. Vascularization was investigated along the tear edges in immature menisci. Glycosaminoglycans and type 2 collagen deposition were negatively affected in immature menisci. We observed glycosaminoglycan degradation in mature menisci and cartilage degeneration, specifically in immature cartilage of the femoral condyle. In conclusion, compared with mature rabbits, immature rabbits showed more robust healing response after untreated meniscal tears. Vascularization contributed to the recellularization after meniscal tears in immature menisci. Meniscal injury fundamentally alters extracellular matrix deposition.