Background: We investigated the impact of 1) passive heating (PH) induced by single and intermittent/prolonged hot-water immersion (HWI) and 2) the duration of PH, on muscle contractile function under the unfatigued state, and during the development of muscle fatigue. Methods: Twelve young males volunteered for this study consisting of two phases: single phase (SP) followed by intermittent/prolonged phase (IPP), with both phases including two conditions (i.e., four trials in total) performed randomly: control passive sitting (CON) and HWI (44-45°C; water up to the waist level). SP-HWI included one continuous 45-min bath (from 15 to 60 min). IPP-HWI included an initial 45-min bath (from 15 to 60 min) followed by eight additional 15-min baths interspaced with 15-min breaks at room temperature between 75 and 300 min. Intramuscular (Tmu; measured in the vastus lateralis muscle) and rectal (Trec) temperatures were determined. Neuromuscular testing (performed in the knee extensors and flexors) was performed at baseline and 60 min later during SP, and at baseline, 60, 90, 150 and 300 min after baseline during IPP. A fatiguing protocol (100 electrical stimulations of the knee extensors) was performed after the last neuromuscular testing of each trial. Results: HWI increased Tmu and Trec to 38°C-38.5°C (p < 0.05) during both SP and IPP. Under the unfatigued state, HWI did not affect electrically induced torques at 20 Hz (P20) and 100 Hz (P100). However, it induced a shift towards a faster contractile profile during both SP and IPP, as evidenced by a decreased P20/P100 ratio (p < 0.05) and an improved muscle relaxation (i.e., reduced half-relaxation time and increased rate of torque relaxation; p < 0.05). Despite a reduced voluntary activation (i.e., -2.63% ± 4.19% after SP-HWI and -5.73% ± 4.31% after IPP-HWI; condition effect: p < 0.001), HWI did not impair maximal isokinetic and isometric contraction torques. During the fatiguing protocol, fatigue index and the changes in muscle contractile properties were larger after HWI than CON conditions (p < 0.05). Finally, none of these parameters were significantly affected by the heating duration. Conclusion: PH induces changes in muscle contractile function which are not augmented by prolonged exposure when thermal stress is moderate.

This study was designed to develop an understanding of the pathophysiology of traumatic muscle injury in the context of Western diet (WD; high fat and high sugar) and obesity. The objective was to interrogate the combination of WD and injury on skeletal muscle mass and contractile and metabolic function.
Male and female C57BL/6J mice were randomized into four groups based on a two-factor study design: (1) injury (uninjured vs. volumetric muscle loss [VML]) and (2) diet (WD vs. normal chow [NC]). Electrophysiology was used to test muscle strength and metabolic function in cohorts of uninjured + NC, uninjured + WD, VML + NC and VML + WD at 8 weeks of intervention.
VML-injured male and female mice both exhibited decrements in muscle mass (-17%, P < 0.001) and muscle strength (-28%, P < 0.001); however, VML + WD females had a 28% greater muscle mass compared to VML + NC females (P = 0.034), a compensatory response not detected in males. VML-injured male and female mice both had lower carbohydrate- and fat-supported muscle mitochondrial respiration (JO2 ) and less electron conductance through the electron transport system (ETS); however, male VML-WD had 48% lower carbohydrate-supported JO2 (P = 0.014) and 47% less carbohydrate-supported electron conductance (P = 0.026) compared to male VML + NC, and this diet-injury phenotype was not present in females. ETS electron conductance starts with complex I and complex II dehydrogenase enzymes at the inner mitochondrial membrane, and male VML + WD had 31% less complex I activity (P = 0.004) and 43% less complex II activity (P = 0.005) compared to male VML + NC. This was a diet-injury phenotype not present in females. Pyruvate dehydrogenase (PDH), β-hydroxyacyl-CoA dehydrogenase, citrate synthase, α-ketoglutarate dehydrogenase and malate dehydrogenase metabolic enzyme activities were evaluated as potential drivers of impaired JO2 in the context of diet and injury. There were notable male and female differential effects in the enzyme activity and post-translational regulation of PDH. PDH enzyme activity was 24% less in VML-injured males, independent of diet (P < 0.001), but PDH enzyme activity was not influenced by injury in females. PDH enzyme activity is inhibited by phosphorylation at serine-293 by PDH kinase 4 (PDK4). In males, there was greater total PDH, phospho-PDHser293 and phospho-PDH-to-total PDH ratio in WD mice compared to NC, independent of injury (P ≤ 0.041). In females, PDK4 was 51% greater in WD compared to NC, independent of injury (P = 0.025), and was complemented by greater phospho-PDHser293 (P = 0.001).
Males are more susceptible to muscle metabolic dysfunction in the context of combined WD and traumatic injury compared to females, and this may be due to impaired metabolic enzyme functions.

Cancer cachexia is clinically defined by involuntary weight loss >5% in <6 mo, primarily affecting skeletal muscle. Here, we aimed to identify sex differences in the onset of colorectal cancer cachexia with specific consideration to skeletal muscle contractile and metabolic functions. Eight-weeks old BALB/c mice (69 males, 59 females) received subcutaneous C26 allografts or PBS vehicle. Tumors were developed for 10-, 15-, 20-, or 25 days. Muscles and organs were collected, in vivo muscle contractility, protein synthesis rate, mitochondrial function, and protein turnover markers were assessed. One-way ANOVA within sex and trend analysis between sexes were performed, P < 0.05. Gastrocnemius and tibialis anterior (TA) muscles became atrophic in male mice at 25 days, whereas female mice exhibited no significant differences in muscle weights at endpoints despite presenting hallmarks of cancer cachexia (fat loss, hepatosplenomegaly). We observed lowered muscle contractility and protein synthesis concomitantly to muscle mass decay in males, with higher proteolytic markers in muscles of both sexes. mRNA of Opa1 was lower in TA, whereas Bnip3 was higher in gastrocnemius after 25 days in male mice, with no significant effect in female mice. Our data suggest relative protections to skeletal muscle in females compared with males despite other canonical signs of cancer cachexia and increased protein degradation markers; suggesting we should place onus upon nonmuscle tissues during early stages of cancer cachexia in females. We noted potential protective mechanisms relating to skeletal muscle contractile and mitochondrial functions. Our findings underline possible heterogeneity in onset of cancer cachexia between biological sexes, suggesting the need for sex-specific approaches to treat cancer cachexia.NEW & NOTEWORTHY Our study demonstrates biological-sex differences in phenotypic characteristics of cancer cachexia between male and female mice, whereby females display many common characteristics of cachexia (gonadal fat loss and hepatosplenomegaly), protein synthesis markers alterations, and common catabolic markers in skeletal muscle despite relatively preserved muscle mass in early-stage cachexia compared with males. Mechanisms of cancer cachexia appear to differ between sexes. Data suggest need to place onus of early cancer cachexia detection and treatment on nonmuscle tissues in females.

We have previously demonstrated that acute ingestion of inorganic nitrate (NO3-)-rich beetroot juice (BRJ), a source of nitric oxide (NO) via the NO3- → nitrite (NO2-) → NO pathway, can improve muscle speed and power in older individuals. It is not known, however, whether this effect is maintained or perhaps even enhanced with repeated ingestion, or if tolerance develops as with organic nitrates, e.g., nitroglycerin. Using a double-blind, placebo-controlled, crossover design, we therefore studied 16 community-dwelling older (age 71 ± 5 y) individuals after both acute and short-term (i.e., daily for 2 wk) BRJ supplementation. Blood samples were drawn and blood pressure was measured periodically during each ∼3 h experiment, with muscle function determined using isokinetic dynamometry. Acute ingestion of BRJ containing 18.2 ± 6.2 mmol of NO3- increased plasma NO3- and NO2- concentrations 23 ± 11 and 2.7 ± 2.1-fold over placebo, respectively. This was accompanied by 5 ± 11% and 7 ± 13% increases in maximal knee extensor speed (Vmax) and power (Pmax), respectively. After daily supplementation for 2 wk, BRJ ingestion elevated NO3- and NO2- levels 24 ± 12 and 3.3 ± 4.0-fold, respectively, whereas Vmax and Pmax were 7 ± 9% and 9 ± 11% higher than baseline. No changes were observed in blood pressure or in plasma markers of oxidative stress with either acute or short-term NO3- supplementation. We conclude that both acute and short-term dietary NO3- supplementation result in similar improvements in muscle function in older individuals. The magnitudes of these improvements are sufficient to offset the decline resulting from a decade or more of aging and are therefore likely to be clinically significant.

Background: We investigated the impact of moderate muscle cooling induced by single and intermittent/prolonged cold-water immersions (CWI) on muscle force and contractility in unfatigued state and during the development of fatigue resulting from electrically induced contractions. Methods: Twelve young males participated in this study consisting of two phases [single phase (SP) followed by intermittent/prolonged phase (IPP)], with both phases including two conditions (i.e., four trials in total) performed randomly: control passive sitting (CON) and cold-water immersions (10°C). SP-CWI included one 45 min-bath (from 15 to 60 min). IPP-CWI included three baths (45 min-bath from 15 to 60 min, and 15 min-baths from 165 to 180 min and from 255 to 270 min), with participants sitting at room temperature the rest of the time until 300 min. Blood pressure and intramuscular (Tmu) temperature were assessed, and neuromuscular testing was performed at baseline and 60 min after baseline during SP, and at baseline, 60, 90, 150 and 300 min after baseline during IPP. A fatiguing protocol (100 electrical stimulations) was performed after the last neuromuscular testing of each trial. Results: In unfatigued state, SP-CWI and IPP-CWI reduced electrically induced torque at 100 Hz (P100) but not at 20 Hz (P20), and increased P20/P100 ratio. The changes from baseline for P100 and P20/P100 ratio were lower in IPP-CWI than SP-CWI. Both cold-water immersion conditions slowed down muscle contraction and relaxation, and reduced maximal isokinetic contraction torque, but the changes from baseline were lower after IPP-CWI than SP-CWI. cold-water immersions did not impair maximal voluntary isometric contraction. During the fatiguing protocol, torque fatigue index and the changes in muscle contractile properties were larger after IPP-CWI than SP-CWI, but were in the same range as after CON conditions. The differences of muscle contractile function between SP-CWI and IPP-CWI were accompanied by a lower reduction of superficial Tmu and a smaller increase in systolic blood pressure after IPP-CWI than SP-CWI. Conclusion: IPP-CWI induces a less pronounced fast-to-slow contractile transition compared to SP-CWI, and this may result from the reduced vasoconstriction response and enhanced blood perfusion of the superficial muscle vessels, which could ultimately limit the reduction of superficial Tmu.

UNASSIGNED: Following the c In the management of BPH, Tamsulosin is an example of a-adrenergic receptor blocker drug that is usually used. In addition, dutasteride is also a BPH drug that works as a group of 5 a reductase inhibitor. However, the weakness of long-term administration of a1-adrenergic receptor antagonists can result in upregulation of prostate smooth muscle cell contractility and expression of a-adrenergic mRNA receptors, resulting in hyperactivity and supersensitivity to a-agonists.
UNASSIGNED: Our study aimed to determine the effect of long-term administration of tamsulosin, dutasteride and tamsulosin-dutasteride combination on the contractility of prostate smooth muscle cells in BPH model rats.
UNASSIGNED: This study was designed using an experimental post test only method, control group design. It measured the contractility of prostate smooth muscle cells from samples obtained from the prostatic stroma of experimental animals adult male Rattus norvegicus Wistar strain induced BPH and administered tamsulosin 1 mg/kg/day, dutasteride 0.5 mg/kg/day, and a combination of continuous administration for 1, 6 and 12 consecutive days. Data were analyzed using one way ANOVA if the data distribution was normal or Kruskall Walis if the data distribution was abnormal.
UNASSIGNED: The effect of tamsulosin, dutasteride and the combination of tamsulosin with dutasteride on prostate smooth muscle cell contractility in experimental animals Rattus norvegicus Wistar strain showed that tamsulosin administration for six days, twelve days, and the combination of tamsulosin dutasteride for one day got statistically significant different result (p=0.016; p=0.006; p=0.029) compared to the negative control group. In addition, there was a difference between the tamsulosin and dutasteride combination group for 12 days compared to tamsulosin monotherapy for 6 days and 12 days (p=0.160; p=0.010).
UNASSIGNED: Continuous administration of monotherapy tamsulosin has an upregulation effect on the sixth to twelfth day. Decreased contractility of prostate smooth muscle cells occurs on the first day but will increase on the sixth to twelfth day. On the other hand, the results of our study also showed that the combination of tamsulosin and dutasteride gave the effect of reducing contractility and was most effective on day 12.

Mao Jian Tea (MJT) has been generally consumed as a digestive aid for more than a hundred years in the Shanxi province of China. However, determination of its efficacy still remains elusive. This study investigated the effect of Mao Jian Green Tea (MJGT) on gastrointestinal motility. The biphasic effects of the hydro extracts of MJGT on gastric emptying and small intestinal propulsion of rats were identified in vivo; namely, the low (MJGT_L) and medium (MJGT_M) concentrations promoted gastrointestinal motility (p < 0.05), whereas the high concentration (MJGT_H) showed the opposite effect (p < 0.01). The expression levels of the gastric hormones, GAS, MTL and VIP (p < 0.05) were consistent with the gastrointestinal motility variation, with the exception of MTL in MJGT_H group (p > 0.01). Two flavonoids, eriodictyol (0.152 mg/mL) and luteolin (0.034 mg/mL), and the corresponding glycosides eriodictyol-7-O-glucoside (0.637 mg/mL) and luteolin-7-O-glucoside (0.216 mg/mL), dominated the hydro extracts identified by HPLC and UPLC-ESI-MS. These compounds can regulate the muscle strip contractions isolated from the gastrointestinal tissues. Additionally, the different concentrations also influenced the gut microbiota accordingly characterized by 16S rDNA gene sequencing. The MJGT_L boosted several probiotic bacteria, such as Muribaculaceae (1.77-fold), Prevotellaceae (1.85-fold) and Lactobacillaceae (2.47-fold), and suppressed the pathogenic species such as Staphylococcaceae (0.03-fold) that, conversely, was enriched in the MJGT_H group (1.92-fold). Therefore, the biphasic effect indicated that the dosage of the herbal tea should not be overlooked.

Aging is associated with skeletal muscle strength decline and cardiac diastolic dysfunction. The structural arrangements of the sarcomeric proteins, such as myosin binding protein-C (MyBP-C) are shown to be pivotal in the pathogenesis of diastolic dysfunction. Yet, the role of fast (fMyBP-C) and slow (sMyBP-C) skeletal muscle MyBP-C remains to be elucidated. Herein, we aimed to characterize MyBP-C and its paralogs in the fast tibialis anterior (TA) muscle from adult and old mice. Immunoreactivity preparations showed that the relative abundance of the fMyBP-C paralog was greater in the TA of both adult and old, but no differences were noted between groups. We further found that the expression level of cardiac myosin binding protein-C (cMyBP-C), an important modulator of cardiac output, was lowered by age. Standard SDS-PAGE along with Pro-Q Diamond phosphoprotein staining did not identify age-related changes in phosphorylated MyBP-C proteins from TA and cardiac muscles; however, it revealed that MyBP-C paralogs in fast skeletal and cardiac muscle were highly phosphorylated. Mass spectrometry further identified glycogen phosphorylase, desmin, actin, troponin T, and myosin regulatory light chain 2 as phosphorylated myofilament proteins in both ages. MyBP-C protein-bound carbonyls were determined using anti-DNP immunostaining and found the carbonyl level of fMyBP-C, sMyBP-C, and cMyBP-C to be similar between old and adult animals. In summary, our data showed some differences regarding the MyBP-C paralog expression and identified an age-related reduction of cMyBP-C expression. Future studies are needed to elucidate which are the age-driven post-translational modifications in the MyBP-C paralogs.

Intestinal failure (IF) occurs when intestinal surface area or function is not sufficient to support digestion and nutrient absorption. Human intestinal organoid (HIO)-derived tissue-engineered intestine is a potential cure for IF. Research to date has demonstrated successful HIO transplantation (tHIO) into mice with significant in vivo maturation. An area lacking in the literature is exploration of murine host sex as a biological variable (SABV) in tHIO function. In this study, we investigate murine host SABV in tHIO epithelial barrier function and muscle contractility. HIOs were generated in vitro and transplanted into nonobese diabetic, severe combined immunodeficiency gamma chain deficient male and female mice. tHIOs were harvested after 8-12 weeks in vivo. Reverse transcriptase polymerase chain reaction and immunohistochemistry were conducted to compare tight junctions and contractility-related markers in tHIOs. An Ussing chamber and contractility apparatus were used to evaluate tHIO epithelial barrier and muscle contractile function, respectively. The expression and morphology of tight junction and contractility-related markers from tHIOs in male and female murine hosts is not significantly different. Epithelial barrier function as measured by transepithelial resistance, short circuit current, and fluorescein isothiocyanate-dextran permeability is no different in tHIOs from male and female hosts, although these results may be limited by HIO epithelial immaturity and a short flux time. Muscle contractility as measured by total contractile activity, amplitude, frequency, and tension is not significantly different in tHIOs from male and female hosts. The data suggest that murine host sex may not be a significant biological variable influencing tHIO function, specifically epithelial barrier maintenance and muscle contractility, though limitations exist in our model.

BACKGROUND: To understand the relationship between myocardial contractility and external stimuli, detecting ex vivo myocardial contractility is necessary.
METHODS: We elaborated a method for contractility detection of isolated C57 mouse papillary muscle using Myostation-Intact system under different frequencies, voltages, and calcium concentrations.
RESULTS: The results indicated that the basal contractility of the papillary muscle was 0.27 ± 0.03 mN at 10 V, 500-ms pulse duration, and 1 Hz. From 0.1 to 1.0 Hz, contractility decreased with an increase in frequency (0.45 ± 0.11-0.10 ± 0.02 mN). The voltage-initiated muscle contractility varied from 3 to 6 V, and the contractility gradually increased as the voltage increased from 6 to 10 V (0.14 ± 0.02-0.28 ± 0.03 mN). Moreover, the muscle contractility increased when the calcium concentration was increased from 1.5 to 3 mM (0.45 ± 0.17-1.11 ± 0.05 mN); however, the contractility stopped increasing even when the concentration was increased to 7.5 mM (1.02 ± 0.23 mN).
CONCLUSIONS: Our method guaranteed the survivability of papillary muscle ex vivo and provided instructions for Myostation-Intact users for isolated muscle contractility investigations.