Bioelectrical impedance analysis cannot be used to measure muscle mass in some individuals. We aimed to determine cutoff values for low skeletal muscle mass index in sarcopenia diagnosis, based on the fat-free muscle mass index estimated using body fat percentage prediction equations, without relying on bioelectrical impedance analysis.

The study included 564 residents from Wakasa, Fukui Prefecture, with a mean age of 76.0±7.1 years. Body composition assessments using bioelectrical impedance analysis were conducted. Three prediction equations for body fat percentage (Ito et al., Deurenberg et al., and Gallagher et al.'s model for Asians) were applied. The cutoff value of the fat-free muscle mass index corresponding to low skeletal muscle mass index in sarcopenia diagnostic criteria was determined using receiver operating characteristic curves.

Receiver operating characteristic curve analysis showed that the formula by Ito et al. yielded the highest area under the curve for estimating low skeletal muscle mass index in men, at 0.83. In women, the formulas by Ito et al. and Gallagher et al. performed similarly, each achieving an area under the curve of 0.779.

The fat-free muscle mass index estimated using the body fat prediction formulas appear to be useful for screening low skeletal muscle mass index.

Levosimendan, a calcium sensitizer, has cardioprotective effects against myocardial ischemia-reperfusion injury (MIRI). Mitophagy plays an important role in MIRI, and the cGAS-STING signaling pathway can participate in mitophagy in a variety of ways. The purpose of this study was to explore the new molecular mechanism by which levosimendan exerts cardioprotective effects in order to provide a new experimental basis for the clinical application of levosimendan. In this study, an isolated MIRI rat model was established, and 48 rats were randomly divided into four groups (n=12): continuous perfusion group (Group C), ischemia-reperfusion group (IR group), ischemia-reperfusion+levosimendan group (IR + L group), and ischemia-reperfusion+ levosimendan+sting activator group (IR+LA group). The hemodynamic indices, myocardial infarction volume, expression of cGAS-STING signaling pathway proteins, and mitophagy-related proteins in isolated rat hearts of the four groups were compared. This study showed that levosimendan can reduce the level of myocardial mitophagy in ischemia-reperfusion rats by inhibiting the cGAS-STING signaling pathway, reducing myocardial injury, and playing a myocardial protective role.

The intestinal barrier represents the first line of host defense. Its dysfunction, defined as increased intestinal permeability, is widely recognized as an important factor in the clinical manifestation of various diseases. Consequently, maintenance of the intestinal barrier is necessary for human health. Caenorhabditis elegans has recently been used frequently as a model organism in studies of gut bacteria – host interactions and in screening for probiotics and prebiotics that promote gut health. Nevertheless, no quantitative method for evaluating the intestinal permeability of Caenorhabditis elegans has yet been established. This study assesses a newly developed evaluation method to assess the intestinal permeability of Caenorhabditis elegans quantitatively using liposomes encapsulating fluorescein isothiocyanate-dextran. The usefulness of this method was confirmed by measuring the intestinal permeability of Pseudomonas aeruginosa-infected or oxidative-stress-induced worms. Furthermore, our method found that agaro-oligosaccharides, the hydrolysis products of agarose, have a beneficial function of preventing increased intestinal permeability. This approach can expand the utility of Caenorhabditis elegans for functional food discovery and drug candidate screening, with specific examination of their effects on gut function.

Ulcerative colitis (UC) is a debilitating inflammatory bowel disease that poses significant challenges in clinical management. Despite existing therapies, many patients fail to achieve adequate symptom relief, underscoring the need to address the underlying mechanisms contributing to the pathogenesis of UC. Andrographis paniculata has been extensively studied in traditional Chinese medicine for its anti-inflammatory properties. This study aimed to evaluate the effects of CX-10, a derivative of andrographolide, on autophagy, oxidative stress, and inflammation in UC. Using dextran sulfate sodium (DSS)-induced mouse model of UC, our findings demonstrated that CX-10 treatment resulted in significant reductions in body weight loss, Disease Activity Index (DAI), and histopathological injury scores, characterized by decreased inflammatory cell infiltration and mucosal damage compared to DSS-treated controls. Quantitative real-time PCR (qRT-PCR) revealed a marked restoration of autophagy-related genes Becn1 and Atg5 in CX-10-treated colonic tissues. Western blot analysis further confirmed enhanced autophagic flux, evidenced by significant increases in the LC3-II/I ratio. CX-10 treatment also led to reduced endoplasmic reticulum (ER) stress, indicated by decreases in the transcript and protein levels of GRP78 and CHOP. Consistent with the in vivo findings, in vitro studies demonstrated that CX-10 effectively enhanced autophagy and reduced oxidative stress in lipopolysaccharides (LPS)-treated HT-29 colonic epithelial cells and RAW 264.7 macrophages. This was accompanied by a marked decrease in reactive oxygen species (ROS) levels, as determined by DCFDA assays. In conclusion, CX-10 exerts protective effects against DSS-induced UC through modulation of autophagy and oxidative stress pathways, suggesting its potential as a novel therapeutic agent for managing UC.

Background

Chemotherapy resistance is a key obstacle in the treatment of triple-negative breast cancer (TNBC). Single-cell RNA sequencing (scRNA-seq) plays a pivotal part in revealing the mechanism of drug resistance in tumors. This work aimed to explore the molecular events driving TNBC resistance based on scRNA-seq data.

Methods

Breast cancer (BC) scRNA-seq data GSE176078 was sourced from the GEO database. Nine TNBC samples were analyzed. The cellular composition and differentially expressed genes of TNBC were clarified through dimension reduction, clustering, and cell annotation. Drug-resistant and sensitive epithelial cell clusters in malignant epithelial cells were identified, with their heterogeneity analyzed. Key genes driving drug-resistant epithelium were screened and KEGG enrichment analysis was undertaken. The expression of UCHL1 in TNBC was examined. The effect and molecular mechanism of UCHL1 on cisplatin (CDDP) resistance in TNBC was confirmed by constructing CDDP-resistant cell lines.

Results

We successfully identified resistant and sensitive cell clusters in malignant epithelial cells of TNBC and screened for the greatly upregulated gene UCHL1 in the resistant epithelium. KEGG analysis revealed its enrichment in the ferroptosis signaling pathway. Further analyses demonstrated the upregulation of UCHL1 in CDDP-resistant TNBC cells. Knocking down UCHL1 potentiated the sensitivity of TNBC cells to CDDP treatment and reinforced ferroptosis. The ferroptosis inhibitor Ferrostatin-1 reversed the inhibitory effect of UCHL1 knockdown on CDDP resistance.

Conclusion

UCHL1 reinforces CDDP resistance in TNBC by suppressing ferroptosis. The study brings new insights into the drug-resistance mechanism of TNBC.

Microglia, the primary immune cells of the central nervous system, play a pivotal role in maintaining brain homeostasis. Recent studies have highlighted the involvement of microglial dysfunction in the pathogenesis of various age-related neurodegenerative diseases, such as Alzheimer’s disease. Moreover, the metabolic state of microglia has emerged as a key factor in these diseases. Interestingly, aging and neurodegenerative diseases are associated with impaired mitochondrial function and a metabolic shift from oxidative phosphorylation to glycolysis in microglia. This metabolic shift may contribute to sustained microglial activation and neuroinflammation. Furthermore, the leakage of mitochondrial DNA into the cytoplasm, because of mitochondrial dysfunction, has been implicated in triggering inflammatory responses and disrupting brain function. This review summarizes recent advances in understanding the role of microglial metabolic shifts, particularly glycolysis and mitochondrial dysfunction. It also explores the potential of targeting microglial metabolism, for instance by modulating mitophagy or intervening in specific metabolic pathways, as a novel therapeutic approach for changes in brain function and neurodegenerative diseases associated with aging.

Piceatannol is a type of polyphenol that is abundantly obtained from passion fruit. The present study aimed to determine the effect of 7 days of piceatannol supplementation on fat metabolism at rest, during and after low-intensity aerobic exercise. This randomized, double-blind, and crossover study included eight physically active male participants. The participants completed two experimental trials: placebo and piceatannol. They ingested either a placebo or piceatannol tablets containing 0 or 10 mg of piceatannol for seven consecutive days. The participants visited the laboratory at 8:00 am after seven days. In the following baseline measurements, the participants performed 60 min of pedaling exercise at 30% of their maximum oxygen uptake. Respiratory gas and blood samples were collected before, during, and after the exercise. No significant differences were found between the trials in oxygen uptake, carbon dioxide output, ventilation, and respiratory exchange ratio either at rest and during and after exercise. Similarly, serum growth hormone, cortisol, insulin, free fatty acid, glycerol, acetoacetic acid, 3-hydroxybutyric acid, and ketone body responses exhibited no significant differences between trials. These results indicate that the 7-day piceatannol supplementation did not promote fat metabolism at rest and during and after low-intensity aerobic exercise.

Lung adenocarcinoma (LUAD) is responsible for a substantial portion of cancer-related deaths, carrying a bleak treatment outlook. The application of ferroptosis-focused treatments has shown great potential. This research is committed to uncovering the molecular mechanisms by which Nei Like DNA Glycosylase 3 (NEIL3) impacts ferroptosis in LUAD, in the quest for robust biomarkers. Using The Cancer Genome Atlas database, qRT-PCR, and western blot (WB), we evaluated the expression of NEIL3 in LUAD tissues and cells, then performed gene set enrichment analysis to identify enriched gene sets. Predictive tools hTFtarget and MoLoTool assisted in identifying potential upstream transcription factors and their promoter binding sites for NEIL3, following which we conducted Pearson correlation analysis. The binding affinity of NEIL3 to Forkhead box protein M1 (FOXM1) was validated with dual-luciferase and chromatin immunoprecipitation assays. Cell viability was determined by measuring MDA and Fe²⁺ content in cells with the aid of cell counting kit-8. Lipid reactive oxygen species (ROS) levels were detected by flow cytometry, and WB was employed to evaluate the expression of GPX4 and SLC7A11 proteins. An upregulation of NEIL3 is observed in LUAD tissues and cell lines, particularly within pathways linked to ferroptosis. When NEIL3 was knocked down, there was a decline in the viability of LUAD cells, coupled with elevated MDA, Fe²⁺, and lipid ROS levels. Protein expression of GPX4 and SLC7A11 was inhibited, but these phenotypes were rescued by the application of a ferroptosis inhibitor. FOXM1 could interact with the NEIL3 gene promoter, initiating its transcription. In the context of LUAD, the activation of NEIL3 by FOXM1 constitutes the FOXM1/NEIL3 axis that counteracts ferroptosis in LUAD cells.

Age-related decrease in joint flexibility leads to difficulties in activities of daily living and an increased risk of falls. The current study investigated whether nerve-directed stretching, which focuses on stretching neural tissue, could acutely improve joint flexibility and tissue stiffness more than muscle-directed stretching or not. Twenty-seven older men performed muscle- and nerve-directed stretching for 400 s (40 s × 10 times) on separate days. Before and after stretching, maximum ankle dorsiflexion angle was measured as range of motion (ROM). Shear wave propagation velocity (SWV) was also assessed as tissue stiffness of the sciatic nerve, medial gastrocnemius, posterior thigh fascia, and posterior leg fascia in anatomical position. In both stretching conditions, increment of ROM and reduction of sciatic nerve SWV were observed after stretching. The extent of these changes did not differ between the stretching conditions. The SWVs of tissues other than the sciatic nerve did not change before and after the stretching. These results suggest that acute effects of nerve-directed stretching on joint flexibility and tissue stiffness are not superior to muscle-directed stretching.

Prolonged compression restricts blood flow, which can result in an insufficient supply of the oxygen and nutrients that are necessary for cells to live and thrive. A pressure ulcer (PU) is a pathological condition of prolonged ischemia and is associated with a loss of epidermis, which could expose the dermis and deeper tissues. It is necessary to remove the causative pressure and resume blood flow, but injurious damage to the ischemic area could occur with a delay after blood reflow, which could result in reperfusion injury. In the early stages of compression, muscle cells, which are highly dependent on aerobic respiration, are preferably damaged, and then the injury could spread to other dermal and epithelial cells. Infiltrated leukocytes release a variety of substances such as cytokines and reactive oxygen species (ROS) that act as anti-microorganisms, but these could also aggravate inflammation. The ROS are deeply involved in the pathogenesis of this condition, and, hence, antioxidant compounds and enzymes play a vital role in preventing the progression of PUs. We focus on oxidative stress in PUs, which is exacerbated by the actions of ischemia/reperfusion, and we discuss effective prevention and treatment from the perspectives of micronutrients and antioxidants.

The number of eosinophilic esophagitis (EoE) patients has been rapidly increasing worldwide in recent years, though remains relatively lower in Japan. To determine whether Japanese EoE ‍cases have pathogenic differences, microRNA (miRNA) transcriptome analyses of esophageal biopsy specimens from patients with EoE were performed to identify involved miRNAs and the results were compared with those for cases reported in Western countries. Japanese patients with EoE (n = 9) or reflux esophagitis (RE) (n = 4) were enrolled, with the latter serving as controls. Biopsies of esophageal mucosal tissue were performed as a part of an upper gastrointestinal endoscopy, followed by comprehensive miRNA expression analysis (2,588 target human miRNAs) using microarray technology. The EoE patients were then treated with a proton pomp inhibitor, and miRNA expression in the esophagus was compared before and after treatment. Hierarchical cluster analysis findings showed clear differences in miRNA expression patterns between the EoE and RE patients, with increased expression of 13 and decreased expression of 10 miRNAs noted in the EoE cases. These results were then compared with miRNA expression in esophageal mucosa of EoE patients presented in Western reports and the expression profiles were found to be very similar. In addition, changes in expression profiles of several miRNAs before and after treatment were observed in the present EoE patients. miRNA microarray analysis of Japanese EoE patients demonstrated a significant overlap of ‍miRNA expression in comparison with Western patients, indicating that EoE likely represents the same disease among diverse racial populations and shows a consistent pathogenesis worldwide.

Lactococcus lactis subsp. lactis (L. lactis) is a common species of ‍lactic acid bacteria (LAB). There is increasing evidence that probiotic L. lactis ameliorates experimental colitis in mice, whereas few studies have revealed the effects of the para­probiotics, i.e., inactivated forms of bacteria. L. lactis L8 strain is a newly identified plant-derived LAB. The present study aimed to investigate the effects of heat-killed L. lactis L8 on dextran sulfate sodium (DSS)-induced colitis in mice. C57BL/6J mice were orally administered L. lactis L8 for 12 days. Colitis was induced by adding 3.5% DSS to the drinking water for 7 days. Mice were euthanized on day 12, and colon tissues and fecal samples were collected. Results demonstrated that administration of L. lactis L8 alleviated the clinical score of the colitis and the histological abnormalities. Additionally, L. lactis L8 led to a significant reduction in the level of colon tumor necrosis factor (TNF)-α. Administration of L. lactis L8 did not affect the gut microbial structure, whereas it altered the relative abundance of Clostridiaceae and Rikenellaceae in colitis mice. Our findings suggest that paraprobiotic L. lactis L8 has an immunomodulatory effect on intestinal inflammation in mice, providing important insight into the biological function of L. lactis L8.

8-Prenylnaringenin (8-PN) is a prenylflavonoid found in hops (Humulus lupulus L.). It has several beneficial functions, which include the inhibition of bone loss and muscle atrophy. 8-PN is a metabolite of xanthohumol, which can prevent obesity in mice; however, the effect of 8-PN on obesity is still unknown. In the present study, we found that 8-PN prevented obesity in high-fat diet-fed mice. When C57BL6/J male mice were fed 8-PN at 0.0005% or 0.005% with a high-fat diet for 8 weeks, body weight gain, fat accumulation in adipose tissue, and fatty liver induced by the high-fat diet were prevented. In mice fed a high-fat diet and 8-PN, adenosine monophosphate-activated protein kinase (AMPK) was activated in visceral adipose tissue, which was accompanied by decreased expression of a fatty acid synthesis-related factor and increased expression of a mitochondrial biosynthesis-related factor downstream of AMPK. AMPK appeared to be activated by adiponectin secretion, which was associated with increased expression of adipocyte differentiation markers in mice fed a high-fat diet and 8-PN. For the first time, this study shows that 8-PN can prevent obesity in mice and that it is effective at low concentrations that humans could consume in their daily diet.

Neurite degeneration is seen in the early stages of many neurodegenerative diseases, and is strongly related to oxidative damage. Possible mechanisms underlying this morphological change include dysruption of calcium homeostasis, increased membrane oxidation, and destabilization of cytoskeletal proteins. However, the detailed mechanisms leading to neuronal damage has not been elucidated. Calcium plays an important role in neuronal changes caused by oxidative stress. Mitochondria and endoplasmic reticulum (ER) play roles in intracellular calcium storages. One mechanism of neurite degeneration associated with oxidative stress may be related to calcium-mediated interactions between mitochondria and ER. In this study, we evaluated intracellular calcium homeostasis, mitochondria, and ER localization when neurite degeneration was induced in neuroblastoma cells that had extended neurites.

Treatment with hydrogen peroxide (H₂O₂) and the calcium ionophore ionomycin induced mitochondria-dependent superoxide production and membrane oxidation. When examining the involvment of calcium efflux from the ER and mitochondria, treatment with a ryanodine receptor inhibitor ruthenium red significantly reduced intracellular calcium concentrations in ionomycin-treated cells. Electron microscopy in neurite degeneration areas revealed numerous fragmented mitochondria in ionomycin-treated cells, and mitochondrial swelling was observed in the same area of H₂O₂-treated cells. Next, we investigated proteins related to fusion and fission by western blotting. However, mitochondrial dysfunction occurs in both cases and is therefore thought to be associated with neurite degeneration. Our results suggest that H₂O₂ and ionomycin cause neurite degeneration via different mechanisms. Interactions between mitochondria and the ER through unknown crosstalk pathways and calcium transfer may play an important role in maintaining neurite function.

Deficiency of pyridoxal 5'-phosphate (PLP) causes neurological abnormalities. The decline in blood PLP concentration has been associated with the onset of dementia, but no studies have been conducted on Japanese. This study aimed to determine the relationship between serum PLP concentration and Alzheimer's disease in older Japanese individuals. A total of 266 participants, 84 healthy participants, 87 participants with mild cognitive impairment (MCI), and 95 patients with Alzheimer's disease (AD) were randomly selected from those who visited the National Center for Geriatrics and Gerontology for Longevity Sciences. Serum PLP concentration was significantly lower in the AD compared to the NC. Participants were divided into quartiles (Q1-Q4). The relationship between quartiles of serum PLP concentration and cognitive function was analyzed using logistic regression analyses adjusted with covariate factors (sex, age, number of applicable frailty evaluations, APOE4, educational level, albumin, homocysteine, vitamin B₁, B₁₂, and folate). The odds ratios (ORs) for MCI or AD were significantly lower for Q3 and Q4 compared to Q1, and the ORs (95% CI) for Q3 and Q4 were 0.40 (0.16–0.98) and 0.37 (0.13–0.99), respectively. Lower serum PLP concentration is independently related to the incidence of MCI or AD. Further research is needed to clarify the causal relationship.

Early predictive markers of bone resorption are required to plan intervention strategies ensuring a healthy aging. Collagen I C-telopeptide (CTX) as bone activity marker shows a fair biological variability, that cause the lack of a well-defined reference range. Given the well-established role of vitamin D in bone remodeling, the aim of this study was to assess the influence of vitamin D status on the variability of CTX serum levels in 131 pre-menopausal (45-54 years) and 951 post-menopausal women (55-90 years).

Serum CTX and vitamin D levels were assessed, respectively, by ELISA and HPLC determination of 25-hydroxy-vitamin D3.

A significantly negative dependence of CTX on vitamin D3, but not age, was found in the whole study cohort (B=-0.170, p<0.0001). A significantly negative correlation between CTX and vitamin D3 was found both in pre-menopausal (r=-0.2614; p=0.0061) and post-menopausal women (r=-0.2220; p<0.0001), and confirmed in post-menopausal women aged 55 to 59 years (r =-0.2840, p=0.0061), 60 to 64 years (r=-0.2143, p= 0.0129), and 70 to 74 years (r=-0.3078, p<0.0001).

These findings suggest that vitamin D status determination and early vitamin D supplementation may be required in women at higher risk of bone resorption because of the physiologically reduced protective effects of estrogens.

Growing knowledge reveals the association between the gut microbiome and skin, rendering the gut microbiome an appealing potential therapeutic target for atopic dermatitis (AD). In this study, we assessed the effect of partially hydrolyzed guar gum (PHGG) on AD-like symptoms induced by topical 1-Chloro-2,4-dinitrobenzene (DNCB) in BALB/c mice. Four weeks of PHGG feeding prevented the loss of epidermal barrier integrity and epithelial hyperplasia in the AD lesion (p < 0.05, effect size > 0.80), indicating a reduction in AD-like symptoms. According to the postulated mechanism, PHGG ingestion modulates the gut microbiome resulting in enhanced butyrate production (p < 0.05). Butyrate suppresses Th2 function in gut immunity, which is believed to have significance in systemic immune regulation. The lowering of blood Th2 cytokines (IL-4 and IL-10, p < 0.05) in the PHGG-fed group confirmed the existence of such a pathway, and butyrate can possibly be considered to have an indirect involvement in the suppression of Th2 immune response in the AD lesions. These findings encourage support for an association between gut microbiome and skin through the immune system, implying that daily PHGG ingestion may be beneficial for suppressing AD symptoms across the gut-immune-skin axis.

The polymethoxylated flavonoid nobiletin has been shown to have a broad range of biological functions. We found that nobiletin regulates cytokine production from T cells. In this study, we examined the mechanism for enhancement of IL-4 production by nobiletin. We investigated the key molecules for production of IL-4 by deep data-based analysis and we identified nine candidate genes. The mRNA expression levels of c-Maf, Gata-3, Nfat 4, and Pparg genes were significantly elevated by treatment with nobiletin. From RNA sequence analysis, the Th1 and Th2 differentiation pathway was shown to be dominantly affected by nobiletin. Furthermore, molecular network analysis showed that GATA-3 is one of the candidate molecules for enhancement of IL-4 production. Treatment of splenocytes including antigen-presenting cells with nobiletin was sufficient for the induction of IL-4 production from DO11.10 mouse CD4⁺ T cells. Treatment of B cells and dendritic cells with nobiletin induced IL-4 production from CD4⁺ cells. Splenocytes from DO11.10 mice that had been treated with nobiletin produced more IL-4 than did splenocytes from control mice. These results revealed that the polymethxylated flavonoid nobiletin specifically enhanced IL-4 production in vitro and in vivo.

Sarcopenic obesity is associated with metabolic disorders and physical limitations. Intramyocellular lipid (IMCL) accumulation is a critical factor affecting muscle strength, independent of muscle mass, in obesity. While diet plays an important role in regulating IMCL, the effects of specific dietary combinations remain poorly understood. This study examined the effects of different combinations of dietary carbohydrates and fats on skeletal muscle quality and function in obese rats. Female Zucker diabetic fatty rats were fed diets containing either sucrose or palatinose combined with either oleic or linoleic acid for 12 weeks. Body and muscle weights, IMCL content, and grip strength were measured. C2C12 myotubes were treated in vitro with varying concentrations of glucose or insulin, along with fatty acids (oleic acid or linoleic acid), to mimic the exposure of each diet. The diet combining sucrose and linoleic acid (SL) significantly increased IMCL accumulation in the extensor digitorum longus (EDL) muscle and reduced grip strength. A negative correlation was observed between IMCL and grip strength. Cluster of differentiation 36 (CD36) protein levels tended to increase in the EDL of the SL diet-fed group. In vitro experiments demonstrated that high glucose levels combined with linoleic acid increased IMCL and CD36 expression. In conclusion, diets high in sucrose and linoleic acid exacerbate IMCL accumulation and reduce muscle strength in obese rats through hyperglycemia-induced interaction.

Osteoporosis is associated with low bone mineral density and poor bone quality in patients with type 2 diabetes mellitus (T2DM). Reports on the association between serum metabolome and osteoporosis in diabetes mellitus are rare. We aimed to identify osteoporosis-related factors in patients with T2DM. This prospective observational study included 67 patients with T2DM without osteoporosis and 24 patients with T2DM with osteoporosis who were treated with teriparatide. The association between the serum metabolome at baseline and changes in bone mineral density and the bone quality of the lumbar spine and proximal femur over 1 year was evaluated. In the teriparatide-treated group, bone mineral density, young adult mean values, and trabecular bone scores (T-scores) of the lumbar spine significantly increased 1 year after baseline compared with those at baseline. Improvements in these bone assessment indices were significantly higher in the teriparatide-treated group than in the non-treated group. Baseline alkaline phosphatase, bone-specific alkaline phosphatase, and malonic acid levels were significantly negatively correlated with bone mineral density, young adult mean values, and T-scores. Changes in bone mineral density, young adult mean values, and T-score 1 year after baseline were significantly positively correlated with baseline alkaline phosphatase, bone-specific alkaline phosphatase, oxalic acid, and aspartic acid levels in the teriparatide-treated group. Serum oxalic acid and malonic acid levels may be novel markers of osteoporosis. Teriparatide may be more effective in patients with higher baseline serum oxalic acid and aspartic acid levels than in those with lower levels.

Zinc plays a role in immune function. This study aimed to investigate the clinical significance of zinc levels in patients with severe trauma by examining the association between serum zinc levels and infectious complications. Inclusion criteria were hospitalization of 2 weeks or more; Abbreviated Injury Scale score of 3 or more; zinc levels measured on admission and at 2 weeks later. Among the 141 included patients on admission, 136 (96.5%) had zinc deficiency, whereas at two weeks later, serum zinc levels increased significantly, with the number of patients with zinc deficiency decreasing to 31 (22.0%). Between the zinc-deficient group and zinc-sufficient group stratified by serum zinc level at two weeks, there were significant differences in lengths of ICU stay and mechanical ventilation, the complication of infection, and positive blood cultures. Logistic regression showed that zinc level at two weeks after admission were significantly associated with the complication of infection (p=0.03). In addition, Age, initial nutrition, Sequential Organ Failure Assessment score, probability of survival, serum phosphate on admission were highly associated with zinc deficiency at two weeks after admission by logistic regression. In the patients with risk factors on admission, zinc supplementation started on the first day of hospitalization might be beneficial.