Closed-Loop Reflex Responses of the Lateral Ankle Musculature From Various Thresholds During a Lateral Ankle Sprain Perturbation.

CONTEXT: Latency is a reliable temporal metric used to evaluate sensorimotor integration of the fibularis longus (FL) and fibularis brevis (FB) during lateral ankle sprain perturbations. Currently, no clinical recommendations exist to select appropriate thresholds to evaluate the closed-loop reflex response of the lateral ankle musculature. The purpose of this study was to assess threshold value on latency of the FL and FB during an unanticipated inversion perturbation that simulates the mechanism of a lateral ankle sprain. DESIGN: Descriptive laboratory study. METHODS: Twenty healthy adults with no history of lateral ankle sprain injury completed an unanticipated single-leg drop landing onto a 25° laterally inclined force platform from a height of 30 cm. Surface electromyography recorded muscle activity data from the FL and FB during the inversion perturbation. Latency was identified at points where muscle activity exceeded 2, 5, and 10 SD above the average muscle activity 200 milliseconds prior to foot contact, and compared across threshold value using a 1-way analysis of variance (P < .05). RESULTS: The 2 SD threshold was significantly shorter than both 5 SD and 10 SD thresholds for the FL (P < .01) and FB (P < .01). Likewise, the 5 SD threshold was significantly shorter than the 10 SD thresholds for FL (P = .004) and FB (P = .003). CONCLUSIONS: More sensitive thresholds results in a shorter closed-loop reflexive response compared to the more rigorous thresholds. We recommend that selection of the appropriate threshold to identify latency of the lateral ankle musculature should be based on the device used to simulate a lateral ankle sprain and the ankle inversion velocity produced during the ankle inversion perturbation.

Analysis of multiple chronic disease characteristics in middle-aged and elderly South Koreans by exercise habits based on association rules mining algorithm.

BACKGROUND: The term, "multiple chronic diseases" (MCD), describes a patient with two or more chronic conditions simultaneously at the same time. Compared with general chronic diseases, it is linked to poorer health outcomes, more difficult clinical management, and higher medical expenses. Several existing MCD guidelines support a healthy lifestyle including regular physical activities but do not include specific exercise therapy recommendations. This study aimed to understand the prevalence and model of MCD in middle-aged and elderly South Koreans by comparing MCD characteristics with exercise habits, to provide a theoretical basis for the implementation of exercise therapy in these patients. METHODS: The data of 8477 participants aged > 45 years from the "2020 Korean Health Panel Survey" were used to analyze the current status of MCD in the middle-aged and elderly. The Chi-square test for categorical variables and the t-test for continuous variables. the used software was IBM SPSS Statistics 26.0 and IBM SPSS Modeler 18.0. RESULTS: In this study, the morbidity rate of MCD was 39.1%. Those with MCD were more likely to be female (p < 0.001), seniors over 65 years of age (p < 0.001), with low education level, no regular exercise behavior (p < 0.01). Chronic renal failure (93.9%), depression (90.4%), and cerebrovascular disease (89.6%) were the top three diseases identified in patients with MCD. A total of 37 association rules were identified for the group of individuals who did not engage in regular exercise. This equated to 61% more than that of the regular exercise group, who showed only 23 association rules. In the extra association rules, cardiovascular diseases (150%), spondylosis (143%), and diabetes (125%) are the three chronic diseases with the highest frequency increase. CONCLUSIONS: Association rule analysis is effective in studying the relationship between various chronic diseases in patients with MCD. It also effectively helps with the identification of chronic diseases that are more sensitive to regular exercise behaviors. The findings from this study may be used to formulate more appropriate and scientific exercise therapy for patients with MCD.

The Relationship Between Posttraumatic Embitterment Disorder and Stress, Depression, Self-Esteem, Impulsiveness, and Suicidal Ideation in Korea Soldiers in the Local Area.

BACKGROUND: The purpose of this study was to identify the prevalence of posttraumatic embitterment disorder (PTED) among soldiers, and examine its relation to stress, depression, self-esteem, impulsiveness, and suicidal ideation. METHODS: The subjects of this study were 200 soldiers and 197 control subjects, a total of 397 persons. Measurement tools used included the PTED self-rating scale, Stress Response Inventory, Beck Depression Inventory, Rosenberg Self-Esteem Inventory, Barratt Impulsiveness Scale, and Beck Scale of Suicide Ideation. RESULT: The major findings of the analysis are as follows: first, 11.5% of the soldiers were in the risk group for PTED, and 4% of them had PTED. Second, PTED in the soldiers was significantly associated with a number of variables such as their educational background, stress, depression, self-esteem, impulsiveness, and suicidal ideation, while it was not significantly associated with age. Third, through the hierarchical multiple regression analysis, it was found that academic background, stress, and depression had a statistically significant positive effect on the incidence of PTED in the soldiers. CONCLUSION: In order to prevent and effectively intervene in PTED in soldiers, there is a need for interventional efforts focused on depression and stress related to negative life events.

Endurance exercise-mediated metabolic reshuffle attenuates high-caloric diet-induced non-alcoholic fatty liver disease.

INTRODUCTION AND AIM: Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases in the United States. Metabolic distress (obese diabetes) is the main causative element of NAFLD. While there is no cure for NAFLD, endurance exercise (EEx) has emerged as a therapeutic strategy against NAFLD. However, mechanisms of EXE-induced hepatic protection especially in female subjects remain unidentified. Thus, the aim of the study is to examine molecular mechanisms of EXE-induced hepatic protection against diet-induced NAFLD in female mice. MATERIAL AND METHODS: Nine-week-old female C57BL/6J mice were randomly divided into three groups: normal-diet control group (CON, n=11); high-fat diet/high-fructose group (HFD/HF, n=11); and HFD/HF+EEx group (HFD/HF+EEx, n=11). The mice assigned to HFD/HF and HFD/HF+EEx groups were fed with HFD/HF for 12 weeks, after which the mice assigned to the EEx group began treadmill exercise for 12 weeks, with HFD/HF continued. RESULTS: EEx attenuated hepatic steatosis, reduced de novo lipogenesis (reduction in ATP-Citrate- Lyase and diacylglycerol-O-acyltransferase 1), and enhanced mitochondrial biogenesis and fatty-acid activation (oxidative phosphorylation enzymes and Acyl-CoA synthetase1). Also, EEx prevented upregulation of gluconeogenic proteins (glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phosphatase, and phosphoenolpyruvate-carboxykinase1), premature senescence (suppression of p53, p22, and p16, tumor-necrosis-factor-α, and interleukin-1ß, and oxidative stress), and autophagy deficiency. Furthermore, EXE reversed apoptosis arrest (cleaved cysteine-dependent-aspartate-directed protease3 and Poly-(ADP-ribose)-polymerase1). CONCLUSION: EEx-mediated reparations of metabolic and redox imbalance (utilization of pentose phosphate pathway), and autophagy deficiency caused by metabolic distress critically contribute to preventing/delaying severe progression of NAFLD. Also, EEx-induced anti-senescence and cell turnover are crucial protective mechanisms against NAFLD.

Loss of MCL-1 leads to impaired autophagy and rapid development of heart failure.

Myeloid cell leukemia-1 (MCL-1) is an anti-apoptotic BCL-2 protein that is up-regulated in several human cancers. MCL-1 is also highly expressed in myocardium, but its function in myocytes has not been investigated. We generated inducible, cardiomyocyte-specific Mcl-1 knockout mice and found that ablation of Mcl-1 in the adult heart led to rapid cardiomyopathy and death. Although MCL-1 is known to inhibit apoptosis, this process was not activated in MCL-1-deficient hearts. Ultrastructural analysis revealed disorganized sarcomeres and swollen mitochondria in myocytes. Mitochondria isolated from MCL-1-deficient hearts exhibited reduced respiration and limited Ca(2+)-mediated swelling, consistent with opening of the mitochondrial permeability transition pore (mPTP). Double-knockout mice lacking MCL-1 and cyclophilin D, an essential regulator of the mPTP, exhibited delayed progression to heart failure and extended survival. Autophagy is normally induced by myocardial stress, but induction of autophagy was impaired in MCL-1-deficient hearts. These data demonstrate that MCL-1 is essential for mitochondrial homeostasis and induction of autophagy in the heart. This study also raises concerns about potential cardiotoxicity for chemotherapeutics that target MCL-1.

Elevation of hepatic autophagy and antioxidative capacity by endurance exercise is associated with suppression of apoptosis in mice.

INTRODUCTION AND OBJECTIVES: Endurance exercise (EXE) has emerged as a potent inducer of autophagy essential in maintaining cellular homeostasis in various tissues; however, the functional significance and molecular mechanisms of EXE-induced autophagy in the liver remain unclear. Thus, the aim of this study is to examine the signaling nexus of hepatic autophagy pathways occurring during acute EXE and a potential crosstalk between autophagy and apoptosis. MATERIALS AND METHODS: C57BL/6 male mice were randomly assigned to sedentary control group (CON, n=9) and endurance exercise (EXE, n=9). Mice assigned to EXE were gradually acclimated to treadmill running and ran for 60min per day for five consecutive days. RESULTS: Our data showed that EXE promoted hepatic autophagy via activation of canonical autophagy signaling pathways via mediating microtubule-associated protein B-light chain 3 II (LC3-II), autophagy protein 7 (ATG7), phosphorylated adenosine mono phosphate-activated protein kinase (p-AMPK), CATHEPSIN L, lysosome-associated membrane protein 2 (LAMP2), and a reduction in p62. Interestingly, this autophagy promotion concurred with enhanced anabolic activation via AKT-mammalian target of rapamycin (mTOR)-p70S6K signaling cascade and enhanced antioxidant capacity such as copper zinc superoxide dismutase (CuZnSOD), glutathione peroxidase (GPX), and peroxiredoxin 3 (PRX3), known to be as antagonists of autophagy. Moreover, exercise-induced autophagy was inversely related to apoptosis in the liver. CONCLUSIONS: Our findings indicate that improved autophagy and antioxidant capacity, and potentiated anabolic signaling may be a potent non-pharmacological therapeutic strategy against diverse liver diseases.

Intestinal Flukes Recovered from a Herring Gull, Larus argentatus, in the Republic of Korea.

Trematode specimens were collected from the intestine of a herring gull, Larus argentatus, which was found in a critical condition on the shore of a small island (Yubu-do, Seocheon-gun, Chungcheongnam-do) located at the western coast of the Korean peninsula. Total 11 specimens of intestinal flukes, including 3 Cryptocotyle lingua (Heterophyidae), 1 Himasthla alincia (Echinostomatidae), 5 Cardiocephaloides medioconiger (Strigeidae), and 2 Diplostomum spathaceum (Diplostomidae), were recovered. C. lingua was morphologically characterized by the presence of a large ventrogenital apparatus and 2 obliquely tandem testes. H. alincia had an elongated body and a head collar equipped with 31 collar spines. C. medioconiger had a bisegmented body and a voluminous copulatory bursa containing the seminal vesicle and ejaculatory duct. D. spathaceum also had a bisegmented body and its vitellaria extended up to the anterior border of the tribocytic organ. It is of note that C. lingua is potentially zoonotic that can occur in birds and humans. Three of them, i.e., C. lingua, C. medioconiger, and D. spathaceum, are new trematode fauna in Korea. Studies on trematode fauna of migratory birds should be continued in Korea.

Infections of Soil-Transmitted Helminth in Refugees from North Korea.

Soil-transmitted helminthiases (STH) are now no longer public health problems in the Republic of Korea (South Korea), but their status are unavailable in the residents of North Korea (NK) despite the expectation of large scale traffic and future reunification of the Korean Peninsula. A total of 20 female refugees from NK who had been admitted to the Division of Gastroenterology, Dankook University Hospital, were subjected in this study. Among them, 15 refugees were examined by the colonoscopy and 10 ones were examined with the stool examination (formalin-ether sedimentation). Both diagnostic methods were commonly adopted in 5 patients. Eggs of Trichuris trichiura were detected in 7 out of 10 refugees in the stool examination. In the colonoscopy, T. trichiura worms were found in 6 (40.0%) out of 15 refugees. Total 9 (45.0%) peoples were confirmed to be infected with human whipworms. Additionally, 1 case of clonorchiasis was diagnosed in the stool examination and a worm of Ascaris lumbricoides was discovered from a trichuriasis case. These findings suggested that STH is highly prevalent in NO, in which living conditions are not so good in the aspect of general hygiene and medical care.

Novel interactions between erythroblast macrophage protein and cell migration.

Erythroblast macrophage protein is a novel protein known to mediate attachment of erythroid cells to macrophages to form erythroblastic islands in bone marrow during erythropoiesis. Emp-null macrophages are small with round morphologies, and lack cytoplasmic projections which imply immature structure. The role of Emp in macrophage development and function is not fully elucidated. Macrophages perform varied functions (e.g. homeostasis, erythropoiesis), and are implicated in numerous pathophysiological conditions such as cellular malignancy. The objective of the current study is to investigate the interaction of Emp with cytoskeletal- and cell migration-associated proteins involved in macrophage functions. A short hairpin RNA lentiviral system was use to down-regulate the expression of Emp in macrophage cells. A cell migration assay revealed that the relocation of macrophages was significantly inhibited when Emp expression was decreased. To further analyze changes in gene expression related to cell motility, PCR array was performed by down-regulating Emp expression. The results indicated that expression of mitogen-activated protein kinase 1 and thymoma viral proto-oncogene 1 were significantly higher when Emp was down-regulated. The results implicate Emp in abnormal cell motility, thus, warrants to assess its role in cancer where tumor cell motility is required for invasion and metastasis.

Recovery of Oswaldotrema nacinovici from Whimbrels (Aves) in Korea.

Adult specimens of Oswaldotrema nacinovici (Digenea: Philophthalmidae) have been first identified in Korea from 2 migratory birds (whimbrels, Numenius phaeopus) which were found dead at a western seashore area near Gunsan. The worms were recovered in the intestine of these birds. The worms were morphologically characterized by a large ventral sucker in comparison to the oral sucker, an external seminal vesicle extending beyond the posterior margin of the ventral sucker, and conspicuous uterine seminal receptacle. It was noteworthy that metacercariae-like bodies were contained within the inflated regions of 2 ceca. Other intestinal trematode species found in whimbrels included Spelotrema pygmeum, Gynaecotyla squatarolae, Maritrema obstipum, and Himasthla megacotyle. Zoonotic potential of these trematode species should be taken into considerations.

Cellular redox status determines sensitivity to BNIP3-mediated cell death in cardiac myocytes.

The atypical BH3-only protein Bcl-2/adenovirus E1B 19-kDa interacting protein 3 (BNIP3) is an important regulator of hypoxia-mediated cell death. Interestingly, the susceptibility to BNIP3-mediated cell death differs between cells. In this study we examined whether there are mechanistic differences in BNIP3-mediated cell death between neonatal and adult cardiac myocytes. We discovered that BNIP3 is a potent inducer of cell death in neonatal myocytes, whereas adult myocytes are remarkably resistant to BNIP3. When exploring the potential underlying basis for the resistance, we discovered that adult myocytes express significantly higher levels of the mitochondrial antioxidant manganese superoxide dismutase (MnSOD) than neonatal myocytes. Overexpression of MnSOD confers resistance to BNIP3-mediated cell death in neonatal myocytes. In contrast, the presence of a pharmacological MnSOD inhibitor, 2-methoxyestradiol, results in increased sensitivity to BNIP3-mediated cell death in adult myocytes. Cotreatment with the mitochondria-targeted antioxidant MitoTEMPO or the MnSOD mimetic manganese (III) tetrakis (4-benzoic acid) porphyrin chloride abrogates the increased cell death by 2-methoxyestradiol. Moreover, increased oxidative stress also restores the ability of BNIP3 to induce cell death in adult myocytes. Taken together, these data indicate that redox status determines cell susceptibility to BNIP3-mediated cell death. These findings are clinically relevant, given that pediatric hearts are known to be more vulnerable than the adult heart to ischemic injury. Our studies provide important insight into why pediatric hearts are more sensitive to ischemic injury and may help in the clinical management of childhood heart disease.

Frontal branch of the superficial temporal artery: anatomical study and clinical implications regarding injectable treatments.

BACKGROUND: The frontal branch of the superficial temporal artery (Fbr) is vulnerable to damage triggered by iatrogenic manipulation by both dermal filler and BoNT-A injection. The purpose of this study was to elucidate the branching pattern of Fbr and to determine its location and course on the lateral border of the frontal belly of the occipitofrontalis muscle (FB). METHODS: Sixty-four hemifaces from 38 Korean cadavers (26 males and 12 females; mean age 71.9 years) were dissected, and the location and course of the Fbr were identified with reference to the lateral border of the FB. RESULTS: The ramification of the frontal branch from the superficial temporal artery (STA) occurred 36.9 ± 14.24 mm (mean ± SD) superior and 17.2 ± 8.2 mm anterior to the posterior-most point of the tragus [i.e., tragion (Tg)]. The Fbr was observed as a single branch in 96.9% of cases and reached its destination at a single point in 71.9%. It reached the Fbr 14.8 ± 7.7 mm superior to the uppermost point of the eyebrow and 15.8 ± 9.1 mm from the lateral epicanthus. The Fbr bifurcated into superior and inferior branches before reaching the FB in 25.0% of cases. In two cases (3%), the Fbr ramified from the STA within 1 mm of the Tg. The diameter of the superior division of Fbr was 1.6 ± 0.5 mm at the lateral border of the FB and 1.8 ± 0.6 mm at other locations. CONCLUSION: Physicians performing injection treatments such as botulinum toxin type A and dermal filler injection to the posterior frontal area should be aware of the various distributions of the Fbr.

Parkin protein deficiency exacerbates cardiac injury and reduces survival following myocardial infarction.

It is known that loss-of-function mutations in the gene encoding Parkin lead to development of Parkinson disease. Recently, Parkin was found to play an important role in the removal of dysfunctional mitochondria via autophagy in neurons. Although Parkin is expressed in the heart, its functional role in this tissue is largely unexplored. In this study, we have investigated the role of Parkin in the myocardium under normal physiological conditions and in response to myocardial infarction. We found that Parkin-deficient (Parkin(-/-)) mice had normal cardiac function for up to 12 months of age as determined by echocardiographic analysis. Although ultrastructural analysis revealed that Parkin-deficient hearts had disorganized mitochondrial networks and significantly smaller mitochondria, mitochondrial function was unaffected. However, Parkin(-/-) mice were much more sensitive to myocardial infarction when compared with wild type mice. Parkin(-/-) mice had reduced survival and developed larger infarcts when compared with wild type mice after the infarction. Interestingly, Parkin protein levels and mitochondrial autophagy (mitophagy) were rapidly increased in the border zone of the infarct in wild type mice. In contrast, Parkin(-/-) myocytes had reduced mitophagy and accumulated swollen, dysfunctional mitochondria after the infarction. Overexpression of Parkin in isolated cardiac myocytes also protected against hypoxia-mediated cell death, whereas nonfunctional Parkinson disease-associated mutants ParkinR42P and ParkinG430D had no effect. Our results suggest that Parkin plays a critical role in adapting to stress in the myocardium by promoting removal of damaged mitochondria.

Ru(II)-catalyzed selective C-H amination of xanthones and chromones with sulfonyl azides: synthesis and anticancer evaluation.

A ketone-assisted ruthenium-catalyzed selective amination of xanthones and chromones C-H bonds with sulfonyl azides is described. The reactions proceed efficiently with a broad range of substrates with excellent functional group compatibility. This protocol provides direct access to 1-aminoxanthones, 5-aminochromones, and 5-aminoflavonoid derivatives known to exhibit potent anticancer activity.

The Sihler staining study of the infraorbital nerve and its clinical complication.

The infraorbital nerve (ION) is a cardinal cutaneous nerve that provides general sensation to the mid face. Its twigs are vulnerable to iatrogenic damage during medical and dental manipulations. The aims of this study were to elucidate the distribution pattern of the ION and thus help to prevent nerve damage during medical procedures and to enable accurate prognostic evaluation where complications do occur. This was achieved by treating 7 human hemifaces with the Sihler modified staining protocol, which enables clear visualization of the course and distribution of nerves without the accidental displacement of these structures that can occur during classic dissection. The twigs of the ION can be classified into the usual 5 groups: inferior palpebral, innervating the lower eyelid in a fan-shaped area; external and internal nasal, reaching the nosewing and philtrum including the septal area between the nostrils, respectively; as well as medial and lateral superior labial, supplying the superior labial area from the midline to the mouth corner. Of particular note, the superior labial twigs fully innervated the infraorbital triangle formed by the infraorbital foramen, the most lateral point of the nosewing, and the mouth corner. In the superior 3-quarter area, the ION twigs made anastomoses with the buccal branches of the facial nerve, forming an infraorbital nervous plexus. The infraorbital triangle may be considered a dangerous zone with respect to the risk for iatrogenic complications associated with the various medical interventions such as implant placement.

Recurred sparganosis 1 year after surgical removal of a sparganum in a Korean woman.

Sparganosis, an infection due to the plerocercoid of Spirometra erinacei, are found worldwide but the majority of cases occur in East Asia including Korea. This report is on a recurred case of sparganosis in the subcutaneous tissue of the right lower leg 1 year after a surgical removal of a worm from a similar region. At admission, ultrasonography (USG) of the lesion strongly suggested sparganosis, and a worm was successfully removed which turned out to be a sparganum with scolex. Since sparganum has a variable life span, and may develop into a life-threatening severe case, a patient once diagnosed as sparganosis should be properly followed-up for a certain period of time. Although imaging modalities were useful for the diagnosis of sparganosis as seen in this case, serological test such as ELISA should also be accompanied so as to support the preoperative diagnosis.

Anatomical and histological study of the arterial distribution in the columellar area, and the clinical implications.

PURPOSE: The aim of this study was to elucidate the distribution of the columellar artery (CoA) in the mobile nasal septum by means of detailed dissection and histological observation. METHODS: Fifteen Korean cadavers were examined; five specimens were dissected to observe the ramification pattern of the CoA from the superior labial artery (SLA), and the noses of ten specimens were quick-frozen in isopropanol cooled with liquid nitrogen and then cryosectioned at a thickness of 40 µm. RESULTS: The arterial vasculature of the CoA in the columella was supplied by the SLA and entered the columella via the columellolabial junction. The vessels of the CoA proceeded anteriorly, inferior to the medial crus of the lower lateral cartilage (MC) at the midline, at the basal and posterior portions of the septum. The vessels traveled closer to the MC than the epidermis. There were very few vessels in the area between the left and right MCs, which was usually packed only with loose connective tissue. More anteriorly, there were more abundant vessels between the MC and the epidermis, with a dispersed distribution. In axial sections, multiple vessels were dispersed in front of the MC, with the pattern varying among the specimens. Furthermore, tiny vessels were also detected in the vicinity of the septal cartilage posterior to the MC. The microdistribution near to the MC was almost consistent. CONCLUSION: The anatomical findings of the CoA in this study will be useful for safe manipulations during various medical interventions in the columella.

Voluntary Wheel Running Reduces Cardiometabolic Risks in Female Offspring Exposed to Lifelong High-Fat, High-Sucrose Diet.

PURPOSE: Maternal and postnatal overnutrition has been linked to an increased risk of cardiometabolic diseases in offspring. This study investigated the impact of adult-onset voluntary wheel running to counteract cardiometabolic risks in female offspring exposed to a life-long high-fat, high-sucrose (HFHS) diet. METHODS: Dams were fed either a HFHS or a low-fat, low-sucrose (LFLS) diet starting from 8 weeks prior to pregnancy and continuing throughout gestation and lactation. Offspring followed their mothers' diets. At 15 weeks of age, they were divided into sedentary (Sed) or voluntary wheel running (Ex) groups, resulting in four groups: LFLS/Sed (n = 10), LFLS/Ex (n = 5), HFHS/Sed (n = 6), HFHS/Ex (n = 5). Cardiac function was assessed at 25 weeks, with tissue collection at 26 weeks for mitochondrial respiratory function and protein analysis. Data were analyzed using two-way ANOVA. RESULTS: While maternal HFHS diet did not affect the offspring's body weight at weaning, continuous HFHS feeding post-weaning resulted in increased body weight and adiposity, irrespective of the exercise regimen. HFHS/Sed offspring showed increased left ventricular wall thickness and elevated expression of enzymes involved in fatty acid transport (CD36, FABP3), lipogenesis (DGAT), glucose transport (GLUT4), oxidative stress (protein carbonyls, nitrotyrosine), and early senescence markers (p16, p21). Their cardiac mitochondria displayed lower oxidative phosphorylation (OXPHOS) efficiency and reduced expression of OXPHOS complexes and fatty acid metabolism enzymes (ACSL5, CPT1B). However, HFHS/Ex offspring mitigated these effects, aligning more with LFLS/Sed offspring. CONCLUSIONS: Adult-onset voluntary wheel running effectively counteracts the detrimental cardiac effects of a lifelong HFHS diet, improving mitochondrial efficiency, reducing oxidative stress, and preventing early senescence. This underscores the significant role of physical activity in mitigating diet-induced cardiometabolic risks.

Treadmill exercise represses neuronal cell death and inflammation during Aß-induced ER stress by regulating unfolded protein response in aged presenilin 2 mutant mice.

Alzheimer's disease (AD) is characterized by the deposition of aggregated amyloid-beta (Aß), which triggers a cellular stress response called the unfolded protein response (UPR). The UPR signaling pathway is a cellular defense system for dealing with the accumulation of misfolded proteins but switches to apoptosis when endoplasmic reticulum (ER) stress is prolonged. ER stress is involved in neurodegenerative diseases including AD, but the molecular mechanisms of neuronal apoptosis and inflammation by Aß-induced ER stress to exercise training are not fully understood. Here, we demonstrated that treadmill exercise (TE) prevented PS2 mutation-induced memory impairment and reduced Aß-42 deposition through the inhibition of ß-secretase (BACE-1) and its product, C-99 in cortex and/or hippocampus of aged PS2 mutant mice. We also found that TE down-regulated the expression of GRP78/Bip and PDI proteins and inhibited activation of PERK, eIF2α, ATF6α, sXBP1 and JNK-p38 MAPK as well as activation of CHOP, caspase-12 and caspase-3. Moreover, TE up-regulated the expression of Bcl-2 and down-regulated the expressions of Bax in the hippocampus of aged PS2 mutant mice. Finally, the generation of TNFα and IL-1α and the number of TUNEL-positive cells in the hippocampus of aged PS2 mutant mice was also prevented or decreased by TE. These results showed that TE suppressed the activation of UPR signaling pathways as well as inhibited the apoptotic pathways of the UPR and inflammatory response following Aß-induced ER stress. Thus, therapeutic strategies that modulate Aß-induced ER stress through TE could represent a promising approach for the prevention or treatment of AD.

Direct acylation of N-benzyltriflamides from the alcohol oxidation level via palladium-catalyzed C-H bond activation.

A palladium-catalyzed ortho-acylation of N-benzyltriflamides from the alcohol oxidation level via C-H bond activation is described. These transformations have been applied to a wide range of substrates, and typically proceed with excellent levels of chemoselectivity and with high functional group tolerance.