BACKGROUND:Muscle relaxants reduce "total" oxygen consumption, and 1.2 mg/kg of rocuronium has been shown to attenuate ischemia-reperfusion injury (IRI). Therefore, we herein investigated whether 0.9 mg/kg of rocuronium reduced "local" oxygen consumption and IRI indirectly by measuring changes in hypoxanthine (HPX), an indicator of intracellular adenosine triphosphate (ATP) consumption, and malondialdehyde (MDA), an indicator of IRI, respectively. METHODS:This study was designed as a randomized controlled trial. Female patients aged 50-79 years old who were scheduled for elective knee arthroplasty under general anesthesia were recruited. After the collection of pre-ischemia blood samples, 0.9 mg/kg of rocuronium was administered to patients in group R and a placebo to those in group C 3 minutes before tourniquet inflation. Five minutes after tourniquet deflation, post-ischemia blood samples were collected. The primary outcome was the change in the concentration of MDA (Δ MDA) after ischemia. RESULTS:Medians [interquartile ranges] for Δ MDA (μmol/L) in group R (n = 19) and group C (n = 18) were -0.47 [-1.25 to 0.13] and -0.58 [-0.67 to -0.28], respectively, with no significant difference (p = 0.796). Means ± standard deviations for Δ HPX (μmol/L) were 1.09 ± 0.70 and 1.71 ± 1.09 in groups R and C, respectively, and the difference between the groups was significant (p = 0.046). CONCLUSIONS:We were unable to confirm that 0.9 mg/kg of rocuronium attenuates IRI or postoperative quadriceps muscle weakness. While the present results suggest that rocuronium reduced intracellular ATP consumption, no clinically beneficial effects were observed.
BACKGROUND:In Japan, postnatal care is delivered through follow-up home visits conducted by mother-child nurses in the community employed by local governments. During these visits, the nurses are responsible for promptly assessing the family's circumstances and mother's mental health and determining appropriate directions for ongoing support. This study aimed to determine the characteristics of mothers and children assessed by mother-child nurses in the community as needing ongoing support. METHODS:In this qualitative study, participants were enrolled through convenience sampling. In total, 17 mother-child nurses in the community working at three Japanese local government health centres were surveyed through focus group interviews. RESULTS:The characteristics of mothers and children requiring ongoing support generated 11 categories and 49 subcategories, which were organised into the following six classifications: physical factors of the mother, psychological and emotional factors, socioeconomic factors, social support factors, behavioural factors and physical factors of the child. DISCUSSION:This study revealed that mother-child nurses in the community conducted comprehensive assessments of mothers and children. Understanding their multifaceted characteristics aids in early abuse detection, postpartum depression prevention and maternal mental health promotion. The findings reveal the importance of providing seamless support for mothers and infants, offering valuable insights for mother-child nurses in the community to consider in their care practices.
OBJECTIVES:The International Association for the Study of Lung Cancer (IASLC) proposed a grading system based on predominant histologic subtypes and reflecting prognosis. We previously reported that thyroid transcription factor-1 (TTF-1) expression levels and tumor cell proportion are useful predictors of immunochemotherapy for lung adenocarcinoma. Building upon our previous findings that TTF-1 negativity was associated with poorer outcomes in patients receiving immunochemotherapy, this study further investigated the relationship between TTF-1 expression and IASLC histologic subtypes, and analyzed progression-free survival (PFS) according to TTF-1 expression within each histologic subtype. MATERIALS AND METHODS:We used the same multicenter retrospective dataset as in our previous study, which was conducted between January 2019 and May 2023. TTF-1 was considered positive as a predictive factor of immunochemotherapy when staining showed high TTF-1 expression. The association between TTF-1 expression, histologic subtype, and mucus-producing components was evaluated. RESULTS:Among 95 patients, the positivity rate for TTF-1 was 61.1%. The negative rate of TTF-1 in mucus-producing adenocarcinomas was significantly higher than that in non-mucus-producing adenocarcinomas (18/29 [62.1%] vs. 18/63 [28.6%]; p < 0.01). As per the analysis of IASLC grade 3, the median PFS of TTF-1 negative patients was significantly worse than that of positive patients (6.0 vs. 7.6 months, p = 0.035). Among patients with solid predominant patterns, the median PFS was significantly worse in the patients with TTF-1 negative than positive (5.2 vs. 8.5 months, p = 0.014). CONCLUSION:This study shows that the combination of histopathology and TTF-1 expression is a predictive factor in patients treated with combined immunochemotherapy.
We aimed to compare survival rates in a 4-day-old mouse model of cecal slurry (CS)-induced bacterial peritonitis managed by laparotomy (LAP) or percutaneous peritoneal lavage (PPL). Four-day-old pups received intraperitoneal injections of CS to induce severe (3.0 g/gBW) or mild (1.0 g/gBW) peritonitis. Two hours later, pups underwent either LAP or PPL. Seven-day survival rates, perioperative body temperature (BT) changes, and postoperative ascites and plasma cytokine levels were assessed. In the severe peritonitis group, the 7-day survival rate tended to be higher in pups who underwent PPL than in those who underwent LAP (36.4% vs. 9.1%, p = 0.069). In the mild peritonitis group, survival rates were similar between treatments (83.3% vs. 72.7%, p = 0.53). The median perioperative BT change was significantly smaller in pups who underwent PPL for both the severe (-1.2℃ vs. -2.6℃, p < 0.01) and mild (-0.2℃ vs. -2.9℃, p < 0.01) peritonitis groups. Postoperative tumor necrosis factor levels were significantly lower in the PPL group compared with the LAP group under mild peritonitis (202 pg/ml vs. 443 pg/ml, p = 0.034). We established a novel 4-day-old PPL mouse model and identified PPL as a potential minimally invasive alternative that might help prevent perioperative hypothermia in the fatal peritonitis.
Additional gastrectomy is usually performed after endoscopic submucosal dissection (ESD) for early gastric cancer diagnosed as "non-curative" according to the Japanese guidelines. However, the prognostic benefit of additional gastrectomy for the elderly with non-curative ESD is still debatable. The Geriatric Nutritional Risk Index (GNRI) is known as a prognostic value in elderly patients. This study aimed to clarify the advantages of GNRI as a prognostic indicator for elderly gastric cancer patients with non-curative ESD. A total of 120 elderly patients who underwent ESD for gastric cancer and diagnosed as non-curative resection according to the Japanese guidelines were retrospectively selected from the database of the Kobe University Hospital between January 2008 and March 2020. Their general condition, risk of lymph node metastasis, and nutritional status were evaluated retrospectively, and prognostic analysis was performed. After non-curative ESD, 48 patients underwent additional gastrectomy with lymph node dissection, and 72 patients were followed up with no additional treatment. In the follow-up group, patients with a high risk of lymph node metastasis had a significantly poorer prognosis. However, in the prognostic analysis of 120 cases, additional gastrectomy or follow-up were not independent prognostic factors. In the analysis of the additional gastrectomy group only, major nutrition-related risk of postoperative GNRI was an independent prognostic factor (95% CI: 0.01-0.25, P < 0.001). In elderly, the GNRI may be helpful as a prognostic indicator. Especially for elderly patients with poor nutritional status, additional gastrectomy might be considered only in cases of high risk of recurrence after non-curative ESD.
Effective sucking is important for shortening hospital stays in newborn infants. Several studies have demonstrated that oral support can improve sucking efficiency. However, the effects of oral support on sucking pressure have not been thoroughly investigated. In our previous study, we reported the equipment configuration and analysis method of sucking pressure. That method of measuring sucking pressure was applied to cheek support. In this study, four newborn infants with low birth weight, congenital diaphragmatic hernia, or multicystic encephalomalacia were enrolled. Their sucking pressures were measured during bottle feeding, both with and without cheek support. In all cases, cheek support increased sucking pressure. However, changes in intake volume and the number of sucking bursts, individual sucks did not show a consistent pattern. Our study indicates a possible association between cheek support and sucking pressure during oral feeding in newborn infants. Larger studies are needed to confirm this effect.
Rivaroxaban is an oral, selective, direct-acting factor Xa inhibitor with high affinity for the active site of factor Xa. Thromboelastography (TEG® 6s) has reportedly been used to evaluate coagulation function under rivaroxaban administration, especially in the perioperative period. To date, there are no reports in the literature about thromboelastography in children that have ingested a large amount of rivaroxaban. We describe the case of a 25-month-old girl who accidentally ingested a large dose of rivaroxaban and we followed up on the coagulation performance with TEG® 6s. When she came to our emergency room, there was no apparent bleeding. The patient was hospitalized for observation while undergoing monitoring using TEG® 6s. Approximately 20 h after taking the medication, all values of her blood tests including TEG® 6s returned to the normal range and the patient was discharged, without evidence of bleeding. This case highlights the potential usefulness of TEG® 6s for evaluating the effects of rivaroxaban in pediatric accidental ingestion.
AIM:This study explores the nursing practices of transitional care support for patients with heart failure performed by three different groups of nurses: 1) ward, 2) discharge planning, and 3) visiting nurses. DESIGN:We conducted a qualitative, content analysis. METHODS:Twelve ward nurses, four discharge planning nurses, and five visiting nurses were purposively sampled. Data were collected through semi-structured interviews and analyzed using content analysis. RESULTS:Ward nurses implemented four practices, including "Encourage patients to improve to prevent re-exacerbations" and "Share information with the home care team." Discharge planning nurses implemented four practices, including "Communicate with the home care team to ensure the continued management of heart failure." Visiting nurses implemented three practices, including "Make efforts to obtain test results and, based on physical signs, symptoms, and the pathological condition, detect signs of heart failure exacerbation." CONCLUSION:In transitional care support for patients with heart failure, the three different groups of nurses (ward, discharge planning, and visiting) must multilaterally share information on patients' pathological conditions, the progression of test results, and physical reactions during activities, while continuing to provide support for lifestyle adjustments.
Natural products, particularly those derived from plants, represent a valuable source of bioactive compounds with potential antiviral activity. In this study, we investigated the antiviral activity of Indonesian plants which belong to Artocarpus genus against SARS-CoV-2 using bioassay-guided separation. Plant materials from the Artocarpus genus were successively extracted using hexane, dichloromethane, and methanol, and the antiviral activities were tested against early SARS-CoV-2 variants. Viral inhibition and cytotoxicity were assessed using RT-qPCR, plaque assays, and MTT assays. Among 54 extracts obtained from the leaves and stem bark of 10 species of Artocarpus, four dichloromethane leaf extracts inhibited viral RNA replication and cytopathic effect at a concentration of 10 μg/mL, and did not show cytotoxic effects at a concentration of 100 μg/mL. The most potent extract was dichloromethane leaf extract of Artocarpus heterophyllus (E16) with the 50% inhibitory concentration (IC50) value of 2.46 µg/mL. Separation by vacuum liquid chromatography and open column chromatography yielded E16F4.3 and E16F4.4 which possess potential activity against SARS-CoV-2 with IC50 values of 0.43 µg/mL and 0.28 µg/mL. These subfractions showed less cytotoxicity, with 50% cytotoxic concentration (CC50) values >100 µg/mL. The selective index (SI; CC50/IC50) of E16F4.3 and E16F4.4 were >232.6 and >357.1, respectively. These results indicate that the leaf extract of Artocarpus heterophyllus contains promising drug candidates against SARS-CoV-2.
A machine learning model using Extreme Gradient Boosting (XGBoost) was developed to predict long-term nursing care needs among older adults, based on comprehensive claims and health checkup data from Japan's public insurance system. The model demonstrated strong predictive performance (AUC: 0.878; sensitivity: 0.784; specificity: 0.820) on the test dataset, supporting its use for early identification of high-risk individuals. Key risk factors identified through permutation importance and marginal effect analyses included advanced age, prior care needs, neurological and gastrointestinal diseases, as well as specific medical procedures and medications. In contrast, factors such as joint replacement surgery and the use of preventive care services were associated with lower risk. Lifestyle and biochemical indicators, including slower gait speed and low LDL cholesterol, also significantly influenced risk. Constipation, osteoporosis, and lower back pain had relatively small marginal effects, but was associated with a high incidence rate. This model provides a valuable tool for extending healthy life expectancy and optimizing long-term care planning in aging populations, supporting both public health policy and personalized prevention.
Apolipoprotein B48 (ApoB48) may be an indicator of residual cardiovascular risk beyond conventional lipid measures. However, its performance for detecting coronary artery disease (CAD), alone and in combination with the ankle-brachial index (ABI), remains to be investigated. This cross-sectional study (358 patients; 299 and 59 with and without CAD, respectively) assessed the value of ApoB48 (cutoff: ≥4.5 μg/mL) and ABI (cutoff: <0.9) in detecting CAD. Subgroup analyses were performed for patients with diabetes mellitus, hypertension, dyslipidemia, and low levels of low-density lipoprotein-cholesterol (LDL-C) (<100 mg/dL). Baseline characteristics, including lipid profiles and biomarker levels, were compared between patients with and without CAD. Patients with CAD exhibited significantly higher ApoB48 levels compared to those without (5.1 ± 3.2 vs. 4.0 ± 2.2 μg/mL, respectively, p = 0.001); there were no significant differences in ABI values. The sensitivity and specificity of ABI alone for CAD were 16.7% and 81.4%, respectively, while those for ApoB48 alone were 48.2% and 61.0%, respectively. Combining both markers improved sensitivity to 55.5%, though specificity declined to 47.5%. Subgroup analyses revealed that ApoB48 maintained superior sensitivity across groups with diabetes, hypertension, dyslipidemia, and low levels of LDL-C. Lipid parameters (LDL-C, non-high density lipoprotein-cholesterol, and triglycerides) showed minimal discriminatory power between patients with and without CAD. ApoB48 demonstrates superior sensitivity for CAD detection compared to ABI, particularly in high-risk patients. While combining ApoB48 and ABI enhances sensitivity, it compromises specificity, suggesting the need for balanced diagnostic strategies. ApoB48 may be a valuable marker of residual cardiovascular risk, particularly in patients with well-controlled LDL-C or comorbid metabolic conditions.
We previously demonstrated that interferon-stimulated gene 15 protein (ISG15) plays a role in enhancing hepatitis B virus (HBV) and hepatitis C virus (HCV) infections through the ISGylation of the HBV X protein (HBx) and the HCV NS5A protein. ISGylation is a post-translational modification where ISG15 is covalently attached to target proteins. These findings suggest that targeting ISGylation could be a potential therapeutic strategy for HBV and HCV infections. In this study, we evaluated the antiviral activity of HZ-6d, a quinoline derivative that inhibits HERC5-mediated ISGylation. Our results showed that HZ-6d did not inhibit HBx ISGylation and only modestly suppressed HBV replication in HBV-infected HepG2-NTCP cells and in HBV-replicating cells. Interestingly, HZ-6d also did not affect NS5A-ISGylation, however, it significantly suppressed HCV replication. These observations suggest that HZ-6d exerts its antiviral effects in HCV-replicating cells through mechanisms independent of HERC5-mediated NS5A-ISGylation. Furthermore, HZ-6d strongly activated the p53-mediated apoptosis signaling pathway, as evidenced by increased levels of phosphorylated p53, cleaved caspase-8, and cleaved caspase-3. Notably, activation of caspase-3 has been implicated in the proteolysis of HCV NS5A, indicating that apoptosis-related mechanisms may contribute to HCV suppression. Collectively, our findings suggest that HZ-6d induces antiviral activity against HCV through the p53-mediated apoptosis pathway, rather than by interfering with HERC5-mediated NS5A ISGylation.
AIM:We previously reported that broad-band and specific wavelengths of ultraviolet B (UVB) limit the development of atherosclerosis by augmenting anti-inflammatory immune responses in hypercholesterolemic mice. This study aimed to elucidate the effect of 284 nm UVB on the stabilization of atherosclerotic plaques and the underlying mechanisms. METHODS AND RESULTS:Six- to eight-week-old male LDL receptor-deficient (Ldlr -/-) mice were fed a high-fat and high-cholesterol diet for 8 weeks to form atherosclerotic lesions, and the diet was changed to a standard diet. The mice were subsequently irradiated with 284 nm UVB at 5 kJ/m2 twice weekly for 2 or 4 weeks. The effects of 284 nm UVB irradiation on atherosclerotic plaque size and components and immunoinflammatory responses were evaluated by histological analysis and flow cytometry. Normalization of plasma cholesterol levels did not prevent the development of atherosclerotic lesions in the aortic sinus of UVB-irradiated or nonirradiated mice, whereas it markedly reduced the lipid content in the aortic sinus lesions of these mice, which was more prominent in UVB-irradiated mice. The accumulation of CD4+ T cells in atherosclerotic lesions and aortic immunoinflammatory responses were reduced in UVB-irradiated mice, although no beneficial effects of UVB treatment on macrophage accumulation or collagen content were observed. The plaque-stabilizing effect of UVB treatment was associated with augmented regulatory T cell immune responses in lymphoid tissues. CONCLUSIONS:284 nm UVB irradiation in combination with lipid-lowering therapy improves the stability of atherosclerotic plaques by augmenting anti-inflammatory Treg immune responses. The combination of aggressive lipid-lowering therapies and 284 nm UVB phototherapy may serve as an attractive therapeutic approach for high-risk patients with vulnerable atherosclerotic plaques.
Around 9.4% of infants born in Japan have a low birthweight. While some studies have clarified the developmental progress of very-low-birthweight (VLBW) and extremely-low-birthweight (ELBW) infants at 18 months, less is known about how these children fare in preschool. This study aimed to identify VLBW and ELBW infants without major complications and their behavioral and emotional characteristics as preschoolers compared to their infantile development. Participants were the parents of 28 VLBW and ELBW children without major complications. The Child Behavior Checklist (CBCL) 1.5-5 was administered at ages 3-5, and the results were compared with the Modified Checklist for Autism in Toddlers (M-CHAT). The examination outcomes were assessed at 18-24 months. Of these, 11 had normal scores on all CBCL scales, but the outcomes of the other 17 children were borderline or in the clinical range on either of the CBCL scales. Twenty-one children were screened negative on M-CHAT. Eleven had normal scores on all CBCL scales, but the outcomes of the other 10 children were borderline or in the clinical range on either of the CBCL scales. Seven children screened positive on M-CHAT, and all scored in the borderline or clinical range on either of the CBCL scales. Seven of the 23 M-CHAT items demonstrated relevance between 6 out of 10 CBCL-1.5-5 scales. M-CHAT-positive infants are likely to continue facing behavioral and emotional problems as preschoolers. Even in infants with a negative M-CHAT screening, the underlying problems may become apparent during the preschool years.
Hepatitis C virus (HCV) infection induces chaperone-mediated autophagy (CMA), where the HCV NS5A protein promotes the binding of the molecular chaperone HSC70 to substrate proteins containing a KFERQ motif. HSC70 recognizes this pentapeptide motif and transports substrates to lysosomes for degradation. In this study, we identified a KFERQ motif (324ELLRQ328) in the YAP1 protein, a key regulator of the Hippo pathway, and examined its interaction with HSC70 during HCV infection. To determine whether HSC70 directly binds to this motif, we generated four YAP1 mutants with specific alterations in the KFERQ motif and assessed their binding to HSC70. Among these, the R327A/Q328A mutant showed the greatest reduction in HSC70 binding, indicating that the sequence 324ELLRQ328 functions as the KFERQ motif in YAP1. Further analysis revealed that YAP1 binds to the substrate-binding domain of HSC70. Moreover, shRNA-mediated knockdown of LAMP2A, a critical receptor for CMA, led to increased levels of YAP1, confirming that YAP1 is indeed a CMA substrate. Notably, HSC70 was also found to interact with phosphorylated YAP1 at serine 127 (S127). Although NS5A did not bind directly to YAP1, NS5A expression reduced the binding between YAP1 and HSC70. This suggests that under normal conditions, YAP1 is recognized by HSC70 and degraded via CMA. However, during HCV infection, NS5A interferes with YAP1-HSC70 interaction, preventing YAP1 from being degraded. As a result, YAP1 accumulates in the cytoplasm and subsequently translocates to the nucleus, where YAP1 may activate genes involved in cell proliferation and survival. This mechanism may contribute to HCV-induced pathogenesis.
BACKGROUND AND AIM:Abemaciclib, a CDK4/6 inhibitor, is used for estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Interstitial lung disease (ILD) is a frequent adverse event of abemaciclib, particularly in Asian patients, though limited information is available on its incidence and risk factors. This study aimed to identify the incidence and risk factors of abemaciclib-induced ILD through a single-center retrospective analysis. METHODS:We analyzed ER-positive, HER2-negative inoperable or metastatic breast cancer patients treated with abemaciclib at Kakogawa Central City Hospital between November 1, 2018, and March 31, 2022. At least two respiratory medicine specialists evaluated computed tomography and examined the development of ILD after the initiation of abemaciclib. We conducted univariate analysis to examine factors associated with the development of ILD. RESULTS:Forty-nine patients were analyzed. The median (range) observation period was 27.0 (10-49) months, and the median (range) duration of abemaciclib was 11.0 (1-43) months. Fourteen patients (28.6%) received abemaciclib as a 3rd-line treatment or later. Ten patients (20.4%) were diagnosed with abemaciclib-induced ILD; 7 were diagnosed within 6 months of the initiation of abemaciclib and 3 developed severe ILD during the same period. We identified lung metastasis as a risk factor for the development of ILD (odds ratio = 5.00, 95% confidence interval: 1.15-21.70; p = 0.032). CONCLUSION:The incidence of abemaciclib-induced ILD was 20.4%, which was higher than previously reported values. Today, as abemaciclib is one of the standard treatments for ER-positive, HER2-negative breast cancer, we should be more careful about ILD.
BACKGROUND:Enteral nutrition therapy in the early postoperative period is essential for patients with esophageal cancer following esophagectomy. HINEX® E-gel LC is an oligomeric formula with various nutrients, including dietary fiber pectin. It is expected to reduce symptoms, such as diarrhea, resulting in improved adherence and a decreased rate of weight loss. However, no reports have examined the adherence to or efficacy of nutritional support therapy using HINEX® E-gel LC after esophagectomy. METHODS:This is a single-institution, single-arm phase II trial. We plan to recruit 32 patients with esophageal cancer who have undergone minimally invasive esophagectomy (MIE) and place an enteral feeding tube. Enteral feeding is to be initiated on the second postoperative day, and the patient is to remain on enteral feeding at 300 kcal/day after discharge. The primary endpoint is adherence to enteral nutrition with HINEX® E-gel LC for up to 2 months postoperatively. The secondary endpoint is the association between the adherence to HINEX® E-gel LC and each nutritional parameter, such as hematological examination, body weight, and psoas muscle. DISCUSSION:Although enteral nutrition is usually initiated in the early postoperative period after esophagectomy, the use of fat-containing digestive agents in the early postoperative period is a novel approach. To the best of our knowledge, this study is the first to evaluate the safety and nutritional status of early postoperative enteral nutrition using fat-containing digestive agents after MIE. Efficient nutritional support therapy using fat-containing digestive agents is expected to be especially useful after esophagectomy when oral intake is significantly decreased.
Primary hyperparathyroidism (PHPT) during pregnancy is rare, causing severe pregnancy complications. We report a pregnant woman with PHPT and a pregnancy complication history who underwent a single-gland parathyroidectomy during the second trimester and delivered at term. A 28-year-old pregnant woman, gravida 3, para 2, was referred to our hospital at 9 gestational weeks (GWs) because of previous intrauterine fetal death, preterm birth, and fetal growth restriction. She was diagnosed with PHPT during her second pregnancy, and her baby experienced neonatal hypocalcemia. However, she received no PHPT treatment afterward. Laboratory tests and neck ultrasound revealed hyperparathyroidism and an enlarged right superior parathyroid gland. She underwent a right superior parathyroidectomy at 24 GWs. She delivered a 2,136 g (-1.74 SD) healthy female infant at 37 GWs, and her baby demonstrated no neonatal hypocalcemia. Parathyroidectomy, even during pregnancy, should be considered among pregnant women with PHPT having a pregnancy or neonatal complication history.
We report a rare case of pseudohypercalcemia associated with multiple myeloma in a 77-year-old woman. Despite elevated albumin-corrected calcium levels (12.6 mg/dL), ionized calcium levels remained normal (1.25 mmol/L). Differential diagnoses excluded common causes of hypercalcemia, and the findings suggested calcium binding to negatively charged immunoglobulins and confirmed pseudohypercalcemia due to IgG-type myeloma. Treatment with isatuximab plus dexamethasone normalized albumin-corrected calcium levels as IgG levels decreased. This report highlights the importance of recognizing pseudohypercalcemia to prevent misdiagnosis of true hypercalcemia due to myeloma. Measuring ionized calcium levels is crucial for accurate diagnosis when hypercalcemia is suspected without corresponding clinical symptoms.
Piezo1, a mechanosensitive ion channel that opens in response to mechanical stimuli, is widely expressed among mammalian cell types, and regulates a diverse range of physiological processes. Although evidence has suggested potential clinical benefit of Piezo1 activation for various conditions, the safety and efficacy of such activation in living animals have remained unclear. To investigate the therapeutic potential of Piezo1 activation, we here generated genetically modified mouse models in which Piezo1 is overexpressed either specifically in skeletal muscle or systemically in response to tamoxifen treatment in adult animals. Cast immobilization induced a reduction in both muscle mass and the abundance of Piezo1 mRNA in skeletal muscle of the affected limbs in control mice. Overexpression of Piezo1 in skeletal muscle prevented the immobilization-induced reduction both in soleus muscle mass and in the corresponding cross-sectional area of myofibers, suggesting the potential benefit of Piezo1 activation for prevention of immobilization-induced muscle atrophy. Furthermore, mice with systemic overexpression of Piezo1 showed no apparent abnormalities in growth or general activity. Red blood cells from these mice manifested slight resistance to hypoosmolarity-induced hemolysis, and the animals did not develop apparent hemolytic anemia. Our findings demonstrate promising efficacy and safety of Piezo1 activation in living animals and thereby highlight the therapeutic potential of targeting the Piezo1 signaling pathway.
