A Muscle Energy Techniques-Based Physiotherapeutic Intervention Protocol for Managing Nightstick Fracture: A Case Report.

Distal ulna and radius fractures are the most frequent upper extremity fractures seen in emergency rooms. The axis of rotation for forearm pronation and supination runs through the radial head (proximal) and the ulnar fovea (distal). Throughout pronation and supination, the radius can rotate relative to the ulna, thanks to the way its head articulates with it. The ulna remains relatively stable during these movements. However, in cases of fractures of these bones, surgery to repair the radius is usually the best course of action for a distal ulna fracture. Most distal ulna fractures heal successfully with only conservative treatment once the radius is stabilized. To achieve the best results, medical personnel must take into account patient characteristics including age, level of activity, and aspirations. The majority of distal ulna injuries do not require surgery, but there are several circumstances where it is necessary. In therapeutic practice, muscle energy techniques (METs) are comparatively painless methods for restoring a restricted spectrum of motion. Malunion, reduced grasp, and other significant problems might result from a lack of understanding of this illness. The 48-year-old patient in the present study was reported to have sustained injuries to his left forearm in a road traffic accident (RTA) as he fell from his bike and slid during a traffic collision. X-ray imaging of the left forearm revealed an isolated ulnar shaft fracture. METs, isometric contractions, and active concentric and eccentric movements were all part of the physiotherapy intervention protocol to produce an active range of motion in the upper extremity. In this particular case, the specified physiotherapy management was found to be effective.

Managing Complex Foot Crush Injuries: A Case Report.

A serious kind of fractured foot ailment is a foot crush injury. Foot injury commonly happens in accidents involving transportation or the workplace, such as automobile accidents, big objects falling on the foot, or heavy machinery running over the foot. Foot crush injuries are more severe than regular foot fractures. These wounds are usually very serious, involving many fractures and soft tissue injuries. The main symptoms include pain, severe muscle and tissue damage, and extreme swelling. Because of this, treating a foot crush injury can be quite challenging and frequently requires the collaboration of physical therapists, orthopedic surgeons, and podiatrists. Physiotherapy is important for reducing pain, increasing range of motion, strengthening muscles, and improving leg function. It also decreases the chance of contractures, deformities, and stiffness following crush injuries. In this report, we present the case of a 58-year-old male with a lacerated wound over his left foot with chief complaints of severe pain. Patient-tailored physiotherapy rehabilitation, including active movements, passive movements, isometric exercises, and a strengthening regimen consisting of numerous repetitions and progressive complexity, was given. At the end of four weeks, the patient had improved strength and quality of life.

Src homology 3 domain binding kinase 1 protects against hepatic steatosis and insulin resistance through the Nur77-FGF21 pathway.

BACKGROUND AND AIMS: Metabolism in the liver is dysregulated in obesity, contributing to various health problems including steatosis and insulin resistance. While the pathogenesis of lipid accumulation has been extensively studied, the protective mechanism against lipid challenge in the liver remains unclear. Here, we report that Src homology 3 domain binding kinase 1 (SBK1) is a regulator of hepatic lipid metabolism and systemic insulin sensitivity in response to obesity. APPROACH AND RESULTS: Enhanced Sbk1 expression was found in the liver of high-fat diet (HFD)-induced obese mice and fatty acid (FA)-challenged hepatocytes. SBK1 knockdown in mouse liver cells augmented FA uptake and lipid accumulation. Similarly, liver-specific SBK1 knockout ( Lsko ) mice displayed more severe hepatosteatosis and higher expression of genes in FA uptake and lipogenesis than the Flox/Flox ( Fl/Fl ) control mice when fed the HFD. The HFD-fed Lsko mice also showed symptoms of hyperglycemia, poor systemic glucose tolerance, and lower insulin sensitivity than the Fl/Fl mice. On the other hand, hepatic Sbk1 overexpression alleviated the high-fructose diet-induced hepatosteatosis, hyperlipidemia, and hyperglycemia in mice. White adipose tissue browning was also observed in hepatic SBK1 -overexpressed mice. Moreover, we found that SBK1 was a positive regulator of FGF21 in the liver during energy surplus conditions. Mechanistically, SBK1 phosphorylates the orphan nuclear receptor 4A1 (Nur77) on serine 344 to promote hepatic FGF21 expression and inhibit the transcription of genes involved in lipid anabolism. CONCLUSIONS: Collectively, our data suggest that SBK1 is a regulator of the metabolic adaption against obesity through the Nur77-FGF21 pathway.

Muscle-generated BDNF (brain derived neurotrophic factor) maintains mitochondrial quality control in female mice.

Mitochondrial remodeling is dysregulated in metabolic diseases but the underlying mechanism is not fully understood. We report here that BDNF (brain derived neurotrophic factor) provokes mitochondrial fission and clearance in skeletal muscle via the PRKAA/AMPK-PINK1-PRKN/Parkin and PRKAA-DNM1L/DRP1-MFF pathways. Depleting Bdnf expression in myotubes reduced fatty acid-induced mitofission and mitophagy, which was associated with mitochondrial elongation and impaired lipid handling. Muscle-specific bdnf knockout (MBKO) mice displayed defective mitofission and mitophagy, and accumulation of dysfunctional mitochondria in the muscle when they were fed with a high-fat diet (HFD). These animals also have exacerbated body weight gain, increased intramyocellular lipid deposition, reduced energy expenditure, poor metabolic flexibility, and more insulin resistance. In contrast, consuming a BDNF mimetic (7,8-dihydroxyflavone) increased mitochondrial content, and enhanced mitofission and mitophagy in the skeletal muscles. Hence, BDNF is an essential myokine to maintain mitochondrial quality and function, and its repression in obesity might contribute to impaired metabolism.Abbreviation: 7,8-DHF: 7,8-dihydroxyflavone; ACACA/ACC: acetyl Coenzyme A carboxylase alpha; ACAD: acyl-Coenzyme A dehydrogenase family; ACADVL: acyl-Coenzyme A dehydrogenase, very long chain; ACOT: acyl-CoA thioesterase; CAMKK2: calcium/calmodulin-dependent protein kinase kinase 2, beta; BDNF: brain derived neurotrophic factor; BNIP3: BCL2/adenovirus E1B interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B interacting protein 3-like; CCL2/MCP-1: chemokine (C-C motif) ligand 2; CCL5: chemokine (C-C motif) ligand 5; CNS: central nervous system; CPT1B: carnitine palmitoyltransferase 1b, muscle; Cpt2: carnitine palmitoyltransferase 2; CREB: cAMP responsive element binding protein; DNM1L/DRP1: dynamin 1-like; E2: estrogen; EHHADH: enoyl-CoenzymeA hydratase/3-hydroxyacyl CoenzymeA dehydrogenase; ESR1/ER-alpha: estrogen receptor 1 (alpha); FA: fatty acid; FAO: fatty acid oxidation; FCCP: carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone; FFA: free fatty acids; FGF21: fibroblast growth factor 21; FUNDC1: FUN14 domain containing 1; HADHA: hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha; HFD: high-fat diet; iWAT: inguinal white adipose tissues; MAP1LC3A/LC3A: microtubule-associated protein 1 light chain 3 alpha; MBKO; muscle-specific bdnf knockout; IL6/IL-6: interleukin 6; MCEE: methylmalonyl CoA epimerase; MFF: mitochondrial fission factor; NTRK2/TRKB: neurotrophic tyrosine kinase, receptor, type 2; OPTN: optineurin; PA: palmitic acid; PARL: presenilin associated, rhomboid-like; PDH: pyruvate dehydrogenase; PINK1: PTEN induced putative kinase 1; PPARGC1A/PGC-1α: peroxisome proliferative activated receptor, gamma, coactivator 1 alpha; PRKAA/AMPK: protein kinase, AMP-activated, alpha 2 catalytic subunit; ROS: reactive oxygen species; TBK1: TANK-binding kinase 1; TG: triacylglycerides; TNF/TNFα: tumor necrosis factor; TOMM20: translocase of outer mitochondrial membrane 20; ULK1: unc-51 like kinase 1.

Developing Insulin and BDNF Mimetics for Diabetes Therapy.

Diabetes is a global public health concern nowadays. The majority of diabetes mellitus (DM) patients belong to type 2 diabetes mellitus (T2DM), which is highly associated with obesity. The general principle of current therapeutic strategies for patients with T2DM mainly focuses on restoring cellular insulin response by potentiating the insulin-induced signaling pathway. In late-stage T2DM, impaired insulin production requires the patients to receive insulin replacement therapy for maintaining their glucose homeostasis. T2DM patients also demonstrate a drop of brain-derived neurotrophic factor (BDNF) in their circulation, which suggests that replenishing BDNF or enhancing its downstream signaling pathway may be beneficial. Because of their protein nature, recombinant insulin or BDNF possess several limitations that hinder their clinical application in T2DM treatment. Thus, developing orally active "insulin pill" or "BDNF pill" is essential to provide a more convenient and effective therapy. This article reviews the current development of non-peptidyl chemicals that mimic insulin or BDNF and their potential as anti-diabetic agents.

Muscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility.

The ability of skeletal muscle to switch between lipid and glucose oxidation for ATP production during metabolic stress is pivotal for maintaining systemic energy homeostasis, and dysregulation of this metabolic flexibility is a dominant cause of several metabolic disorders. However, the molecular mechanism that governs fuel selection in muscle is not well understood. Here, we report that brain-derived neurotrophic factor (BDNF) is a fasting-induced myokine that controls metabolic reprograming through the AMPK/CREB/PGC-1α pathway in female mice. Female mice with a muscle-specific deficiency in BDNF (MBKO mice) were unable to switch the predominant fuel source from carbohydrates to fatty acids during fasting, which reduced ATP production in muscle. Fasting-induced muscle atrophy was also compromised in female MBKO mice, likely a result of autophagy inhibition. These mutant mice displayed myofiber necrosis, weaker muscle strength, reduced locomotion, and muscle-specific insulin resistance. Together, our results show that muscle-derived BDNF facilitates metabolic adaption during nutrient scarcity in a gender-specific manner and that insufficient BDNF production in skeletal muscle promotes the development of metabolic myopathies and insulin resistance.

In Silico Approach for SAR Analysis of the Predicted Model of DEPDC1B: A Novel Target for Oral Cancer.

With the incidence rate of oral carcinogenesis increasing in the Southeast-Asian countries, due to increase in the consumption of tobacco and betel quid as well as infection from human papillomavirus, specifically type 16, it becomes crucial to predict the transition of premalignant lesion to cancerous tissue at an initial stage in order to control the process of oncogenesis. DEPDC1B, downregulated in the presence of E2 protein, was recently found to be overexpressed in oral cancer, which can possibly be explained by the disruption of the E2 open reading frame upon the integration of viral genome into the host genome. DEPDC1B mediates its effect by directly interacting with Rac1 protein, which is known to regulate important cell signaling pathways. Therefore, DEPDC1B can be a potential biomarker as well as a therapeutic target for diagnosing and curing the disease. However, the lack of 3D model of the structure makes the utilization of DEPDC1B as a therapeutic target difficult. The present study focuses on the prediction of a suitable 3D model of the protein as well as the analysis of protein-protein interaction between DEPDC1B and Rac1 protein using PatchDock web server along with the identification of allosteric or regulatory sites of DEPDC1B.