Cross-sectional association between high-sensitivity C-reactive protein and cognitive function in community-dwelling older adults: the SONIC study.

BACKGROUND: A decline in cognitive function is associated with inflammatory processes. However, the association between high-sensitivity C-reactive protein (hs-CRP) levels and cognitive decline in the Japanese population remains inconclusive. Thus, this study aimed to determine whether hs-CRP is associated with low cognitive function in 70- and 80-year-old community-dwelling Japanese individuals. METHODS: The participants in this cross-sectional study were 872 Japanese residents aged 70 and 80 years who voluntarily participated in the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians (SONIC) study between 2010 and 2011. Blood sample collection, cognitive assessment, and other measurements were performed at the venue. Low cognitive function was defined as a score of 25 points or lower on the Japanese version of the Montreal Cognitive Assessment. The odds ratio (OR) and 95% confidence interval (95% CI) for each hs-CRP quartile were calculated using logistic regression analysis. RESULTS: A total of 288 (69.9%) parsons in the 70-year-old group and 372 (80.9%) in the 80-year-old group exhibited low cognitive function. The association between hs-CRP levels and low cognitive function was significant among 70- and 80-year-old Japanese community-dwelling adults. In particular, the fourth quartile of hs-CRP (0.727-7.420 mg/L) in the 70-year-old group and the second and fourth quartiles (0.214-0.404 and 0.911-9.890 mg/L) in the 80-year-old group were associated with low cognitive function. Furthermore, the third quartile (0.409-0.892 mg/L) in the 80-year-old group was closely associated with low cognitive function. CONCLUSIONS: High hs-CRP levels were associated with lower cognitive function in 70- and 80-year-old Japanese community-dwelling individuals, suggesting that high hs-CRP levels may influence cognitive function.

Sex differences in reduction of trunk muscle mass related to falls and cognitive function during the COVID-19 pandemic in older adults.

AIM: This study aimed to examine the influence of the COVID-19 pandemic on physical components and activity, and its relationship to physical performance in older adults. METHODS: Sixty-seven participants aged 75 and older (81 ± 2 years, female: 66%), who underwent medical checkups continuously from 2018 to 2022 in one clinic, were enrolled. Muscle mass was assessed by the biometrical impedance analysis method, which was adjusted by height squared. Physical, oral, and cognitive performance data were obtained from Japanese standard questionnaires at medical checkups. Values obtained in 2018 and 2019 were defined as pre-pandemic, and those in 2021 and 2022 were defined as during the pandemic. RESULTS: Body weight, grip strength, and skeletal mass index did not change from 2018 to 2022, but trunk muscle mass index decreased significantly. A difference in the trunk muscle mass index (TMI) was observed between 2022 and 2018/2019 in men; however, a significant difference was found between 2021 and 2022 in women. Compared with the pre-pandemic period, TMI during the pandemic decreased only in men. The difference in TMI between the pre-pandemic period and during the pandemic (ΔTMI) was significantly decreased in participants with low physical activity and poor oral performance before the pandemic, and in those with falls and poor cognitive function during the pandemic only in men. CONCLUSION: Reduction of trunk muscle mass was related to falls and poor cognitive function during the COVID-19 pandemic in older male adults. These data suggest that the difference in response to the COVID-19 pandemic between men and women necessitates different types of support for older adults. Geriatr Gerontol Int 2024; ••: ••-••.

Consensus statement on renal denervation by the Joint Committee of Japanese Society of Hypertension (JSH), Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT), and the Japanese Circulation Society (JCS).

This is the first consensus statement of the Joint Committee on Renal Denervation of the Japanese Society of Hypertension (JSH)/Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT)/Japanese Circulation Society (JCS). The consensus is that the indication for renal denervation (RDN) is resistant hypertension or "conditioned" uncontrolled hypertension, with high office and out-of-office blood pressure (BP) readings despite appropriate lifestyle modification and antihypertensive drug therapy. "Conditioned" uncontrolled hypertension is defined as having one of the following: (1) inability to up-titrate antihypertensive medication due to side effects, the presence of complications, or reduced quality of life. This includes patients who are intolerant of antihypertensive drugs; or (2) comorbidity at high cardiovascular risk due to increased sympathetic nerve activity, such as orthostatic hypertension, morning hypertension, nocturnal hypertension, or sleep apnea (unable to use continuous positive airway pressure), atrial fibrillation, ventricular arrythmia, or heart failure. RDN should be performed by the multidisciplinary Hypertension Renal Denervation Treatment (HRT) team, led by specialists in hypertension, cardiovascular intervention and cardiology, in specialized centers validated by JSH, CVIT, and JCS. The HRT team reviews lifestyle modifications and medication, and the patient profile, then determines the presence of an indication of RDN based on shared decision making with each patient. Once approval for real-world clinical use in Japan, however, the joint RDN committee will update the indication and treatment implementation guidance as appropriate (annually if necessary) based on future real-world evidence.

Consensus statement on renal denervation by the Joint Committee of Japanese Society of Hypertension (JSH), Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT), and the Japanese Circulation Society (JCS).

This is the first consensus statement of the Joint Committee on Renal Denervation of the Japanese Society of Hypertension (JSH)/Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT)/Japanese Circulation Society (JCS). The consensus is that the indication for renal denervation (RDN) is resistant hypertension or "conditioned" uncontrolled hypertension, with high office and out-of-office blood pressure (BP) readings despite appropriate lifestyle modification and antihypertensive drug therapy. "Conditioned" uncontrolled hypertension is defined as having one of the following: 1) inability to up-titrate antihypertensive medication due to side effects, the presence of complications, or reduced quality of life. This includes patients who are intolerant of antihypertensive drugs; or 2) comorbidity at high cardiovascular risk due to increased sympathetic nerve activity, such as orthostatic hypertension, morning hypertension, nocturnal hypertension, or sleep apnea (unable to use continuous positive airway pressure), atrial fibrillation, ventricular arrythmia, or heart failure. RDN should be performed by the multidisciplinary Hypertension Renal Denervation Treatment (HRT) team, led by specialists in hypertension, cardiovascular intervention and cardiology, in specialized centers validated by JSH, CVIT, and JCS. The HRT team reviews lifestyle modifications and medication, and the patient profile, then determines the presence of an indication of RDN based on shared decision making with each patient. Once approval for real-world clinical use in Japan, however, the joint RDN committee will update the indication and treatment implementation guidance as appropriate (annually if necessary) based on future real-world evidence.

Consensus Statement on Renal Denervation by the Joint Committee of Japanese Society of Hypertension (JSH), Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT), and the Japanese Circulation Society (JCS).

This is the first consensus statement of the Joint Committee on Renal Denervation of the Japanese Society of Hypertension (JSH)/Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT)/Japanese Circulation Society (JCS). The consensus is that the indication for renal denervation (RDN) is resistant hypertension or "conditioned" uncontrolled hypertension, with high office and out-of-office blood pressure (BP) readings despite appropriate lifestyle modification and antihypertensive drug therapy. "Conditioned" uncontrolled hypertension is defined as having one of the following: 1) inability to up-titrate antihypertensive medication due to side effects, the presence of complications, or reduced quality of life. This includes patients who are intolerant of antihypertensive drugs; or 2) comorbidity at high cardiovascular risk due to increased sympathetic nerve activity, such as orthostatic hypertension, morning hypertension, nocturnal hypertension, or sleep apnea (unable to use continuous positive airway pressure), atrial fibrillation, ventricular arrythmia, or heart failure. RDN should be performed by the multidisciplinary Hypertension Renal Denervation Treatment (HRT) team, led by specialists in hypertension, cardiovascular intervention and cardiology, in specialized centers validated by JSH, CVIT, and JCS. The HRT team reviews lifestyle modifications and medication, and the patient profile, then determines the presence of an indication of RDN based on shared decision making with each patient. Once approval for real-world clinical use in Japan, however, the joint RDN committee will update the indication and treatment implementation guidance as appropriate (annually if necessary) based on future real-world evidence.

Effects of renal denervation on blood pressure in patients with hypertension: a latest systematic review and meta-analysis of randomized sham-controlled trials.

The efficacy of renal denervation (RDN) has been controversial, but recent randomized sham-controlled trials demonstrated significant blood pressure reductions after RDN in patients with hypertension. We conducted a systematic review and updated meta-analysis to evaluate the effects of RDN on ambulatory and office blood pressures in patients with hypertension. Databases were searched up to 15 November 2023 to identify randomized, sham-controlled trials of RDN. The primary endpoint was change in 24 h ambulatory systolic blood pressure (SBP) with RDN versus sham control. The secondary endpoints were changes in 24 h ambulatory diastolic blood pressure, daytime and nighttime blood pressure (BP), office BP, and home BP. A sub-analysis determined outcomes by medication, procedure, and device. From twelve trials, 2222 patients with hypertension were randomized to undergo RDN (n = 1295) or a sham procedure (n = 927). At 2-6 months after treatment, RDN significantly reduced 24 h ambulatory SBP by 2.81 mmHg (95% confidence interval: -4.09, -1.53; p < 0.001) compared with the sham procedure. RDN also reduced daytime SBP by 3.17 mmHg (- 4.75, - 1.58; p < 0.001), nighttime SBP by 3.41 mmHg (- 4.69, - 2.13; p < 0.001), office SBP by 4.95 mmHg (- 6.37, - 3.54; p < 0.001), and home SBP by 4.64 mmHg (- 7.44, - 1.84; p = 0.001) versus the sham control group. There were no significant differences in the magnitude of BP reduction between first- and second-generation trials, between devices, or between with or without medication. These data from randomized sham-controlled trials showed that RDN significantly reduced all blood pressure metrics in medicated or unmedicated patients with hypertension, including resistant/uncontrolled hypertension.

Effects of multimorbidity and polypharmacy on physical function in community-dwelling older adults: A 3-year prospective cohort study from the SONIC.

BACKGROUND: We prospectively examined the effect of baseline multimorbidity and polypharmacy on the physical function of community-dwelling older adults over a three-year period. METHODS: The analysis included 1,401 older adults (51.5 % women) who participated in both wave 1 and wave 2 (3-year follow-up) of the Septuagenarians, Octogenarians, and Nonagenarians Investigation with Centenarians (SONIC) study. Grip strength and walking speed were binarized into poor/not poor physical function according to the frailty definition. The number of chronic conditions and the number of prescribed medications were categorized into 3 and 4 groups, respectively. Multivariable logistic regression was used to examine associations between the number of chronic conditions, medication use at baseline, and poor physical function over a three-year period. RESULTS: After adjusting for confounding factors, hyperpolypharmacy (≥ 10 medications) demonstrated associations with weak grip strength (adjusted odds ratio [aOR] = 2.142, 95 % confidence interval [CI] = 1.100-4.171) and slow walking speed (aOR = 1.878, 95 % CI = 1.013-3.483), while co-medication (1-4 medications) was negatively associated with slow walking speed (aOR = 0.688, 95 % CI = 0.480-0.986). There was no significant association between the number of chronic conditions and physical function. CONCLUSION: The findings suggest that the number of medications can serve as a simple indicator to assess the risk of physical frailty. Given that many older individuals receive multiple medications for extended durations, medical management approaches must consider not only disease-specific treatment outcomes but also prioritize drug therapy while actively avoiding the progression towards frailty and geriatric syndromes.

Geriatric prognostic scoring system predicts survival after hepatectomy for elderly patients with liver cancer.

Aim: The number of elderly patients with liver cancer is increasing with the aging society. The Geriatric Prognostic Scoring System is useful in predicting the postoperative prognosis for elderly patients with gastrointestinal cancer. The aim of the present study was to assess the predictive ability of the geriatric prognostic scoring system for postoperative survival in elderly patients with liver cancer. Methods: Eighty-eight patients aged ≥75 years who were treated for primary liver cancer and metastatic liver tumor were retrospectively analyzed. The Geriatric Prognostic Score (GPS) was created by several clinical parameters such as age, sex, type of cancer, stage, performance status, body mass index, and comprehensive geriatric assessment. Each patient was divided into two groups of high-risk to low-risk according to their GPS: ≧30 high-risk group and <30 low-risk. The predictive ability of geriatric prognostic scoring system for postoperative survival was assessed in univariate and multivariate analyses. Results: Of the 88 patients, 75 were diagnosed as hepatocellular carcinoma and 13 as colorectal liver metastasis. After geriatric prognostic scoring system assessments, 26 patients were diagnosed as high-risk and the remaining 62 as low-risk. The 3-year overall survival rates were 78.5% in the low-risk group and 35.1% in the high-risk group (p < 0.001). The univariate and multivariate analyses of overall survival identified high GPS as an independent significant factor (p < 0.001). Conclusions: We could conclude that the geriatric prognostic scoring system is useful in predicting patients' prognosis after hepatectomy and it can provide helpful information to surgeons for determining treatment strategies for elderly patients with liver cancer.

Imaging Biomarker for Early-Stage Alzheimer Disease: Utility of Hippocampal Histogram Analysis of Diffusion Metrics.

BACKGROUND AND PURPOSE: Biomarkers have been required for diagnosing early Alzheimer disease. We assessed the utility of hippocampal diffusion parameters for diagnosing Alzheimer disease pathology in mild cognitive impairment. MATERIALS AND METHODS: Sixty-nine patients with mild cognitive impairment underwent both CSF measurement and multi-shell diffusion imaging at 3T. Based on the CSF biomarker level, patients were classified according to the presence (Alzheimer disease group, n = 35) or absence (non-Alzheimer disease group, n = 34) of Alzheimer disease pathology. Neurite orientation dispersion and density imaging and diffusion tensor imaging parametric maps were generated. Two observers independently created the hippocampal region of interest for calculating histogram features. Interobserver correlations were calculated. The statistical significance of intergroup differences was tested by using the Mann-Whitney U test. Logistic regression analyses, using both the clinical scale and the image data, were used to predict intergroup differences, after which group discriminations were performed. RESULTS: Most intraclass correlation coefficient values were between 0.59 and 0.91. In the regions of interest of both observers, there were statistically significant intergroup differences for the left-side neurite orientation dispersion and density imaging-derived intracellular volume fraction, right-side diffusion tensor imaging-derived mean diffusivity, left-side diffusion tensor imaging-derived mean diffusivity, axial diffusivity, and radial diffusivity (P < .05). Logistic regression models revealed that diffusion parameters contributed the most to discriminating between the groups. The areas under the receiver operating characteristic curve for the regions of interest of observers A/B were 0.69/0.68, 0.69/0.68, 0.73/0.68, 0.71/0.68, and 0.68/0.68 for the left-side intracellular volume fraction (mean), right-side mean diffusivity (mean), left-side mean diffusivity (10th percentile), axial diffusivity (10th percentile), and radial diffusivity (mean). CONCLUSIONS: Hippocampal diffusion parameters might be useful for the early diagnosis of Alzheimer disease.

Effects of interleukin-15 on autophagy regulation in the skeletal muscle of mice.

This study aimed to evaluate the role of skeletal muscle-derived interleukin (IL)-15 in the regulation of skeletal muscle autophagy using IL-15 knockout (KO) and transgenic (TG) mice. Male C57BL/6 wild-type (WT), IL-15 KO, and IL-15 TG mice were used in this study. Changes in muscle mass, forelimb grip strength, succinate dehydrogenase (SDH) activity, gene and protein expression levels of major regulators and indicators of autophagy, comprehensive gene expression, and DNA methylation in the gastrocnemius muscle were analyzed. Enrichment pathway analyses revealed that the pathology of IL-15 gene deficiency was related to the autophagosome pathway. Moreover, although IL-15 KO mice maintained gastrocnemius muscle mass, they exhibited a decrease in autophagy induction. IL-15 TG mice exhibited a decrease in gastrocnemius muscle mass and an increase in forelimb grip strength and SDH activity in skeletal muscle. In the gastrocnemius muscle, the ratio of phosphorylated adenosine monophosphate-activated protein kinase α (AMPKα) to total AMPKα and unc-51-like autophagy activating kinase 1 and Beclin1 protein expression were higher in the IL-15 TG group than in the WT group. IL-15 gene deficiency induces a decrease in autophagy induction. In contrast, IL-15 overexpression could improve muscle quality by activating autophagy induction while decreasing muscle mass. The regulation of IL-15 in autophagy in skeletal muscles may lead to the development of therapies for the autophagy-induced regulation of skeletal muscle mass and cellular quality control.NEW & NOTEWORTHY IL-15 gene deficiency can decrease autophagy induction. However, although IL-15 overexpression induced a decrease in muscle mass, it led to an improvement in muscle quality. Based on these results, understanding the role of IL-15 in regulating autophagy pathways within skeletal muscle may lead to the development of therapies for the autophagy-induced regulation of skeletal muscle mass and cellular quality control.

Actual conditions for returning home after hospitalization among older patients receiving home medical care in Japan: OHCARE Study.

AIM: To examine the actual conditions of older patients receiving home medical care after hospitalization over a period of 2 years in Japan. METHODS: The study population included 102 participants, aged ≥65 years, receiving home medical care, who consented to participate in the Osaka Home Care Registry (OHCARE) study in Japan over a period of 2 years. We investigated the actual conditions for returning home after hospitalization. RESULTS: The median age of the 102 participants was 84 years, and 61 (59.8%) were women. In the group that returned home, 42 (55.3%) of the respondents desired to recuperate in a familiar place, as in advanced care planning (ACP). During the 2-year follow-up period, the group that did not return home had significantly more deaths. A multivariate analysis showed the association in the presence of ACP (odds ratio: 4.72, 95% confidence interval: 1.60-13.86) and cardiac disease (odds ratio: 0.25, 95% confidence interval: 0.08-0.76). The lack of ACP in the medical records when the patient was admitted to the hospital may have prevented the return home. CONCLUSION: In older patients who had difficulty returning home after hospitalization, the lack of ACP in home medical care may have been an influencing factor. ACP could help continue with home medical care. Geriatr Gerontol Int 2024; 24: 320-326.

Factors influencing the continuation of home blood pressure measurement in community-dwelling older adults: the NOSE study.

OBJECTIVE: This study aimed to identify the factors influencing home blood pressure measurement (HBPM) continuation in community-dwelling older adults. METHODS: A longitudinal analysis used the NOSE study intervention group datasets. The participants were encouraged HBPM with self-monitoring devices provided to them twice in the morning and twice in the evening. Every 7-day interval from the HBPM start date was defined as 1 week, and the number of HBPMs per week was counted. The first week in which the number of HBPMs was zero was defined as the week in which HBPM was discontinued. Participants who did not experienced discontinuation until the end of the observation period were considered complete survivors in the survival time analysis. RESULTS: Data from 437 participants were included in the analysis. Of these, 120 (27.5%) discontinued HBPM. In univariate analysis, factors significantly associated with HBPM discontinuation included exercise habits [hazard ratio per one unit 0.47; 95% confidence interval (CI) 0.31-0.69], social participation (hazard ratio 0.65; 95% CI 0.42-0.99), MoCA-J score (hazard ratio 0.94; 95% CI 0.90-0.98), and frailty (hazard ratio 5.20; 95% CI 2.87-9.43). In multivariate analysis, factors significantly associated with HBPM discontinuation included sex (hazard ratio 0.55; 95% CI 0.32-0.95; ref. = female individuals), smoking history (hazard ratio 1.69; 95% CI 1.02-2.80), exercise habits (hazard ratio 0.51; 95% CI 0.30-0.85), MoCA-J score (hazard ratio 0.93; 95% CI 0.88-0.98), and frailty (hazard ratio 3.31; 95% CI 1.50-7.29). CONCLUSION: Among community-dwelling older adults, female sex, smoking history, lack of exercise, cognitive decline, and frailty were identified as factors influencing HBPM discontinuation.

Knee Extensor Weakness Potently Predicts Postoperative Outcomes in Older Gastrointestinal Cancer Patients.

OBJECTIVES: Muscle weakness, assessed by grip strength, has been shown to predict postoperative mortality in older patients with cancer. Because lower extremity muscle strength well reflects physical performance, we examined whether lower knee extension muscle strength predicts postoperative mortality better than grip strength in older patients with gastrointestinal cancer. DESIGN: Prospective, observational study in a single institution. SETTING AND PARTICIPANTS: A total of 813 patients (79.0 ± 4.2 years, 66.5% male) aged 65 years or older with gastrointestinal cancer who underwent preoperative evaluation of grip strength and isometric knee extension muscle strength between April 2012 and April 2019 were included. METHODS: The study participants were prospectively followed up for postoperative mortality. Muscle weakness was defined as the lowest quartile of grip strength or knee extension strength (GS-muscle weakness and KS-muscle weakness, respectively). RESULTS: Among the study participants, 176 patients died during a median follow-up of 716 days. In the Kaplan-Meier analysis, we found that patients with both GS-muscle weakness and KS-muscle weakness had a lower survival rate than those without muscle weakness. As expected, higher clinical stages and abdominal and thoracic surgeries compared with endoscopic surgery were associated with increased all-cause mortality. In addition, we found that KS-muscle weakness, but not GS-muscle weakness, was an independent prognostic factor after adjusting for sex, body mass index, cancer stage, surgical technique, and surgical site in the Cox proportional hazard model. CONCLUSIONS AND IMPLICATIONS: In older patients with gastrointestinal cancer, muscle weakness based on knee extension muscle strength can be a better predictor of postoperative prognosis than muscle weakness based on grip strength.

Age Group Differences in the Association Between Sleep Status and Frailty Among Community-Dwelling Older Adults: The SONIC Study.

Objective: We aimed to determine whether the association of sleep status with frailty differs between age groups of older adults. Method: This cross-sectional study was part of the observational Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians (SONIC) study. Subjects were community-dwelling older adults in their 70s and 80s. Frailty was evaluated using the Japanese version of the Cardiovascular Health Study criteria (J-CHS). Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep status. Poor sleep quality was defined as a PSQI global score ≥6. Sleep duration was categorized as short (<6 hr), normal (6-8), and long (>8). We performed multivariable logistic regression to investigate the association between sleep status and frailty separately for each age group adjusted for multiple covariates. Results: In those in their 70s, long sleep duration and sleep medication use were independently associated with frailty. In those in their 80s, poor sleep quality was independently associated with frailty. Conclusions: The association between sleep status and frailty was different between age groups. The findings underscore the importance of incorporating the evaluation of sleep quantity and non-pharmacological therapies in those in their 70s and the evaluation of sleep quality in those in their 80s to help prevent the onset of frailty.

Relationship between the number of teeth, occlusal force, occlusal contact area, and dietary hardness in older Japanese adults: The SONIC study.

PURPOSE: Individuals with impaired masticatory function tend to prefer soft foods, which results in decreased masticatory muscle activity. This study examined the association between the oral condition (number of teeth, occlusal force, and occlusal contact area) and dietary hardness using a daily dietary questionnaire. METHODS: This cross-sectional study evaluated 1841 participants aged 69-71 and 79-81 years. Registered dentists examined the number of teeth, occlusal force, and occlusal contact area. Dietary hardness was defined as the estimated masticatory muscle activity required for a habitual diet. Habitual diet during the preceding month was assessed using a brief self-administered diet history questionnaire. Confounding factors, such as age, sex, socioeconomic status, smoking habits, history of chronic diseases (hypertension, hyperlipidemia, and diabetes), and cognitive function were also evaluated. Multivariate linear regression analyses were performed to assess the association between dietary hardness and each oral condition. RESULTS: Occlusal force (standardized regression coefficients [ß]=0.08, P < 0.01) and occlusal contact area (ß=0.06, P < 0.01) were significantly associated with dietary hardness after adjusting for the confounding factors. Number of teeth was not significantly associated with dietary hardness. In addition, the associations between dietary hardness, sex, and a history of diabetes were stronger than those between dietary hardness and oral factors. CONCLUSIONS: Occlusal force and contact area were significantly associated with dietary hardness as estimated from the masticatory muscle activity using a daily diet questionnaire.

Intradermal administration of DNA vaccine targeting Omicron SARS-CoV-2 via pyro-drive jet injector provides the prolonged neutralizing antibody production via germinal center reaction.

Emerging SARS-CoV-2 Omicron variants are highly contagious with enhanced immune escape mechanisms against the initially approved COVID-19 vaccines. Therefore, we require stable alternative-platform vaccines that confer protection against newer variants of SARS-CoV-2. We designed an Omicron B.1.1.529 specific DNA vaccine using our DNA vaccine platform and evaluated the humoral and cellular immune responses. SD rats intradermally administered with Omicron-specific DNA vaccine via pyro-drive jet injector (PJI) thrice at 2-week intervals elicited high antibody titers against the Omicron subvariants as well as the ancestral strain. Indeed, the Omicron B.1.1.529-specific antibody titer and neutralizing antibody were higher than that of other strains. Longitudinal monitoring indicated that anti-spike (ancestral and Omicron) antibody titers decreased toward 30 weeks after the first vaccination dose. However, neutralization activity remained unaltered. Germinal center formation was histologically detected in lymph nodes in rats immunized with Omicron DNA vaccine. Ancestral spike-specific immune cell response was slightly weaker than Omicron spike-specific response in splenocytes with Omicron-adapted DNA vaccine, evaluated by ELISpot assay. Collectively, our findings suggest that Omicron targeting DNA vaccines via PJI can elicit robust durable antibody production mediated by germinal center reaction against this new variant as well as partially against the spike protein of other SARS-CoV-2 variants.

Effects of luseogliflozin treatment on hyperglycemia-induced muscle atrophy in rats.

Diabetes mellitus is recognized as a risk factor for sarcopenia. Luseogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces inflammation and oxidative stress by improving hyperglycemia, subsequently improving hepatosteatosis or kidney dysfunction. However, the effects of SGLT2 inhibitor on the regulation of skeletal muscle mass or function in hyperglycemia are still unknown. In this study, we investigated the effects of luseogliflozin-mediated attenuation of hyperglycemia on the prevention of muscle atrophy. Twenty-four male Sprague-Dawley rats were randomly divided into four groups: control, control with SGLT2 inhibitor treatment, hyperglycemia, and hyperglycemia with SGLT2 inhibitor treatment. The hyperglycemic rodent model was established using a single injection of streptozotocin, a compound with preferential toxicity toward pancreatic beta cells. Muscle atrophy in streptozotocin-induced hyperglycemic model rats was inhibited by the suppression of hyperglycemia using luseogliflozin, which consequently suppressed hyperglycemia-mediated increase in the levels of advanced glycation end products (AGEs) and activated the protein degradation pathway in muscle cells. Treatment with luseogliflozin can restore the hyperglycemia-induced loss in the muscle mass to some degree partly through the inhibition of AGEs-induced or homeostatic disruption of mitochondria-induced activation of muscle degradation.