Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly termed nonalcoholic fatty liver disease (NAFLD), is a widespread global health concern that affects around 25% of the global ...population. Its influence is expanding, and it is anticipated to overtake alcohol as the leading cause of liver failure and liver-related death worldwide. Unfortunately, there are no approved therapies for MASLD; as such, national and international regulatory health agencies undertook strategies and action plans designed to expedite the development of drugs for treatment of MASLD. A sedentary lifestyle and an unhealthy diet intake are important risk factors. Western countries have a greater estimated prevalence of MASLD partly due to lifestyle habits. Mitochondrial dysfunction is strongly linked to the development of MASLD. Further, it has been speculated that mitophagy, a type of mitochondrial quality control, may be impaired in MASLD. Thyroid hormone (TH) coordinates signals from the nuclear and mitochondrial genomes to control mitochondrial biogenesis and function in hepatocytes. Mitochondria are known TH targets, and preclinical and clinical studies suggest that TH, thyroid receptor β (TR-β) analogs, and synthetic analogs specific to the liver could be of therapeutic benefit in treating MASLD. In this review, we highlight how mitochondrial dysfunction contributes to development of MASLD, and how understanding the role of TH in improving mitochondrial function paved the way for innovative drug development programs of TH-based therapies targeting MASLD.
Cationic agent contrast-enhanced computed tomography (cationic CECT) characterizes articular cartilage ex vivo, however, its capacity to detect post-traumatic injury is unknown. The study objectives ...were to correlate cationic CECT attenuation with biochemical, mechanical and histological properties of cartilage and morphologic computed tomography (CT) measures of bone, and to determine the ability of cationic CECT to distinguish subtly damaged from normal cartilage in an in vivo equine model.
Mechanical impact injury was initiated in equine femoropatellar joints in vivo to establish subtle cartilage degeneration with site-matched controls. Cationic CECT was performed in vivo (clinical) and postmortem (microCT). Articular cartilage was characterized by glycosaminoglycan (GAG) content, biochemical moduli and histological scores. Bone was characterized by volume density (BV/TV) and trabecular number (Tb.N.), thickness (Tb.Th.) and spacing (Tb.Sp.).
Cationic CECT attenuation (microCT) of cartilage correlated with GAG (r = 0.74, P < 0.0001), compressive modulus (Eeq) (r = 0.79, P < 0.0001) and safranin-O histological score (r = −0.66, P < 0.0001) of cartilage, and correlated with BV/TV (r = 0.37, P = 0.0005), Tb.N. (r = 0.39, P = 0.0003), Tb.Th. (r = 0.28, P = 0.0095) and Tb.Sp. (r = −0.44, P < 0.0001) of bone. Mean 95% CI cationic CECT attenuation at the impact site (2215 1987, 2443 Hounsfield Units HUs) was lower than site-matched controls (2836 2490, 3182 HUs, P = 0.036). Clinical cationic CECT attenuation correlated with GAG (r = 0.23, P = 0.049), Eeq (r = 0.26, P = 0.025) and safranin-O histology score (r = −0.32, P = 0.0046).
Cationic CECT (microCT) reflects articular cartilage properties enabling segregation of subtly degenerated from healthy tissue and also reflects bone morphometric properties on CT. Cationic CECT is capable of characterizing articular cartilage in clinical scanners.
Hydrogels that are non-toxic, easy to use, cytocompatible, injectable and degradable are valuable biomaterials for tissue engineering and tissue repair. However, few compounds currently fulfil these ...requirements. In this study, we describe the biological properties of a new type of thermosensitive hydrogel based on low-molecular weight glycosyl-nucleosyl-fluorinated (GNF) compound. This gel forms within 25 min by self-assembly of monomers as temperature decreases. It degrades slowly in vitro and in vivo. It induces moderate chronic inflammation and is progressively invaded by host cells and vessels, suggesting good integration to the host environment. Although human adult mesenchymal stem cells derived from adipose tissue (ASC) cannot adhere on the gel surface or within a 3D gel scaffold, cell aggregates grow and differentiate normally when entrapped in the GNF-based gel. Moreover, this hydrogel stimulates osteoblast differentiation of ASC in the absence of osteogenic factors. When implanted in mice, gel-entrapped cell aggregates survive for several weeks in contrast with gel-free spheroids. They are maintained in their original site of implantation where they interact with the host tissue and adhere on the extracellular matrix. They can differentiate in situ into alkaline phosphatase positive osteoblasts, which deposit a calcium phosphate-rich matrix. When injected into subcutaneous sites, gel-encapsulated cells show similar biological properties as implanted gel-cells complexes. These data point GNF-based gels as a novel class of hydrogels with original properties, in particular osteogenic potential, susceptible of providing new therapeutic solutions especially for bone tissue engineering applications.
The patient demographics collected included: age, gender, housing status, established PCP relationship, diagnosis of mental illness, active substance use, and Care Assessment Need (CAN) score. There ...was a correspondence between substance use and other social circumstances (i.e., mental health problems, homelessness). Patient Demographics Trait Cluster 1 (N=88) Cluster 2 (N=121) Cluster 3 (N=148) Demographics Age (Years) 55.9 54.9-56.8 71.3 70.7-71.9 66.1 65.1-67 Female Gender Identity (%) 8% 4%-16% 1% 1%-1% 8% 5%-14% People of Color Identity (%) 18% 11%-28% 3% 1%-8% 10% 6%-16% Personal Circumstance Documentation of Having a PCP (%) 94% 87%-98% 94% 88%-97% 96% 91%-98% Documentation of Mental Health Problems (%) 66% 55%-75% 38% 30%-47% 75% 66%-80% Documentation of Substance Use Problems (%) 35% 26%-46% 12% 8%-20% 53% 45%-61% Evaluated for Homelessness (%) 64% 53%-73% 79% 71%-86% 78% 70%-84% Evidence of Homelessness (%) 7% 7%-14% 0% 0%-0% 7% 4%-13% CAN Score (%) 43% 43%-43% 34% 34%-34% 79% 79%-79% Interpretation Desert Storm Vietnam, with lower rates of challenging social circumstances.
In the present context, solid waste management from the house level is necessary and useful for reducing the load on the municipal dumpsite. Household composting is the best option to segregate and ...treat the organic waste at house level itself. For this, a uniquely designed shaft for household composter is developed and demonstrated along with processing bin, maturation bin, processing shaft, holding stand and leachate collection system. The processing shaft provides the four necessary actions, namely grinding, churning, turning and aeration in the composter while rotating. During the process of composting, it is found that, after every scheduled rotation of the shaft, the temperature increases inside the material. Because of grinding action of the shaft, the particle size of the final compost is 91.2% material passing from 4 mm sieve. The physical and chemical properties with heavy metals of the final compost, compliance the compost standard as per Indian guideline. The composter is compact, portable, mobile, detachable and cost effective for household organic waste.
Well-defined polystyrene with low polydispersity index having methyl and phenylseleno (-SePh) groups at *a- and *w-chain ends, respectively, was afforded via a controlled/'living' radical ...polymerization using a new initiating system: (1-phenylethyl)seleno benzene 1-PESePh/tertbutyl diphenyl (phenylseleno) silane PhSeSiR3 and absorbing visible light at room temperature. A novel design initiating living radical polymerization in a catalytic fashion is described. The polymer yields and number average molecular weight (Mn) of the resulting polymer increased with reaction time. Further, a linear relationship was found for a plot of Mn versus polymer yield. These results indicate that this polymerization proceeds through a living radical mechanism.
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