This study aimed to examine the
in vivo
and
in vitro
therapeutic effects of glycyrrhizic acid (GA) on steroid-induced osteonecrosis of the femoral head (SONFH), which is caused by the overuse of ...glucocorticoids (GCs). Clinically, we identified elevated oxidative stress (OS) levels and an imbalance in osteolipogenic homeostasis in SONFH patients compared to femoral neck fracture (FNF) patients.
In vivo
, we established experimental SONFH in rats
via
lipopolysaccharides (LPSs) combined with methylprednisolone (MPS). We showed that GA and Wnt agonist-S8320 alleviated SONFH, as evidenced by the reduced microstructural and histopathological alterations in the subchondral bone of the femoral head and the decreased levels of OS in rat models.
In vitro
, GA reduced dexamethasone (Dex)-induced excessive NOX4 and OS levels by activating the Wnt/β-catenin pathway, thereby promoting the osteogenic differentiation of mesenchymal stem cells (MSCs) and inhibiting lipogenic differentiation. In addition, GA regulated the expression levels of the key transcription factors downstream of this pathway, Runx2 and PPARγ, thus maintaining osteolipogenic homeostasis. In summary, we demonstrated for the first time that GA modulates the osteolipogenic differentiation commitment of MSCs induced by excessive OS through activating the Wnt/β-catenin pathway, thereby ameliorating SONFH.
GA can reduce the level of OS induced by excessive GCs through the activation of the Wnt/β-catenin signaling pathway, thereby maintaining the osteolipogenic homeostasis of MSCs.
Heart‐on‐a‐Chip In article 2300719, a 3D anisotropic heart‐on‐achip platform is fabricated by Ling Wang, Wenhua Huang, Yaobin Wu, and co‐workers using a hybrid biofabrication approach that combines ...3D printing and electrospinning. This platform can mimic the structure and function of native heart tissues and evaluate drug‐induced cardiotoxicity.
Background: Surgical sutures for sealing gastric perforations (GP) are associated with severe inflammation and postoperative adhesions. Hydrogel bioadhesives offer a potential alternative for ...sutureless repair of GP; however, their application in minimally invasive surgery is limited due to their prefabricated patch-form, lacking in situ gelation capability. In this study, we emphasized an all-in-one minimally invasive strategy for sutureless repair of acute GP. Methods: an injectable photocurable Janus hydrogel was synthesized, and their ability to seal GP was performed. A rat GP model was used to verify the wound healing and antiadhesion efficiency of hydrogels, and a rabbit GP model was used to verify their laparoscopic feasibility. A fresh human corpse GP model was further employed to verify the user-friendliness of a minimally invasive deliverable (MID) device. A minipig GP model was utilized to evaluate the all-in-one minimally invasive strategy for the treatment of acute GP. Results: Such injectable Janus hydrogel exhibited asymmetric adhesiveness, where the inner-facing side of the hydrogel displays strong sealing and wound healing abilities for GP, while the outward-facing side prevents postoperative adhesion formation. We further developed a minimally invasive deliverable (MID) device integrating hydrogel-delivery parts and photocrosslinking-gelation parts in a laparoscope system. The precise delivery and rapid fluid-tight sealing process of the injectable Janus hydrogel using the MID device for in situ GP repair were demonstrated in a simulated clinical scenario. The in vivo effectiveness of GP sutureless repair was successfully validated in porcine models, with further exploration of the underlying mechanism. Conclusions: Our findings reveal that the injectable Janus hydrogel offers an all-in-one strategy for sutureless GP repair and concurrent prevention of postoperative adhesion formation by incorporating the MID device in minimally invasive surgery, presenting the significant potential to reduce patient surgical complications.
In this study, novel antimicrobial peptides had been derived by enzymatic hydrolysis of filefish (Thamnaconus modestus) byproduct (HFBP). Different proteases, (papain P, trypsin T, neutrase N, pepsin ...PE, and the mixture I PN and mixture II PT) and different hydrolysis time (60, 120, 180, and 240 min), have been used to generate peptides with different lengths and amino acid sequences. The antimicrobial properties of HFBPs were tested, against Gram-positive and Gram-negative strains, using disc diffusion method. HFBP prepared after 120 min of the enzymatic hydrolysis by trypsin (HFBP-T) exhibited greatest antibacterial activities. Bacillus cereus 10451 (BC) and Salmonella enteritidis 10982 (SE) strains were most sensitive to HFBP-T with an inhibitory zone of 24.68 and 29.67 mm diameter and minimum inhibitory concentration of 1.25 and 2.5 mg/mL, respectively. Moreover, the antimicrobial activities of tested HFBPs increased significantly at low pH and temperature. The amino acid analysis showed that HFBP-T protein hydrolysate is high in an amino acid of proline, which probably contributes to the antimicrobial activity. The results obtained from scanning electron microscopy suggested that HFBPs might kill bacteria by acting on the cell wall of bacteria. Conclusively, the HFBP derived from filefish byproduct with biological activates is an interesting alternative to the use of waste from the fishing industry as natural antimicrobials in food stuff.
•Hypertriglyceridemia-induced acute pancreatitis recurrence rate is high.•High triglyceride (TG) level post attack is closely associated with recurrence.•Controlling TG below 5.65 mmol/L may be an ...effective strategy to prevent recurrence.•Glucose should be controlled below 7.0 mmol/L for preventing recurrence.•Long-term TG lowering drugs treatment decreases recurrence.
Data on recurrent hypertriglyceridemia-induced acute pancreatitis (HTG-AP) are scarce.
To investigate the incidence and risk factors for recurrence of HTG-AP, and the effect of triglyceride (TG) lowering drugs post index attack on recurrence.
This study was a prospective cohort study of adult patients with first episode of HTG-AP from December 2019 to February 2021 who were followed until recurrence or death, or February 2022. The cumulative incidence function and Fine and Gray's competing-risk model were applied to the analyses.
A total of 317 patients were enrolled, and the 12-month and 18-month cumulative recurrence incidences were 8% and 22%, respectively. The cumulative recurrence incidence was 2 times higher in patients whose serum TG levels post index attack were ≥5.65 mmol/L (subdistribution hazard ratio SHR, 2.00; 95% confidence interval CI, 1.05–3.80; P = 0.034) compared to patients with TG <5.65 mmol/L. The recurrence rate was 3.3 times higher in patients whose glucose levels post index attack were ≥7.0 mmol/L (SHR, 3.31; 95% CI, 1.56–7.03; P = 0.002) than in patients with glucose <7.0 mmol/L). Compared to TG lowering drugs for less than 1 month post index attack, treatment for longer than 12 months decreased the incidence of recurrence by 75% (SHR, 0.25; 95% CI, 0.08–0.80; P = 0.019).
The HTG-AP recurrence incidence is high and closely associated with high levels of TGs and glucose post index attack. Long-term TG lowering drugs treatment significantly decreases this recurrence.
This study aimed to evaluate the safety, efficacy, and feasibility of the rituximab, fotemustine, pemetrexed, and dexamethasone (R-FPD) regimen followed by whole-brain radiotherapy (WBRT) for ...patients with primary central nervous system lymphoma (PCNSL).
A prospective, single-center phase II clinical trial was conducted. Patients with PCNSL newly diagnosed at the First Affiliated Hospital of Zhengzhou University between July 2018 and July 2020 were studied. The R-FPD regimen consisted of rituximab (375 mg/m
i.v. on D0), fotemustine (100 mg/m
i.v. on D1), pemetrexed (600 mg/m
i.v. on D1), and dexamethasone (40 mg i.v. on D1-5). Patients 60 years or younger who showed a complete response (CR) were treated with 23.4 Gy of WBRT after the end of chemotherapy; those older than 60 years with CR were treated with a wait-and-see approach; and those who did not show CR after the 4th cycle of chemotherapy were given salvage WBRT 30 Gy + local tumor field irradiation up to 45 Gy, regardless of age.
A total of 30 patients were included. After 2 cycles, the objective response rate (ORR) was 96.5% (28/29, 1 CR, 27 PR, 0 SD, and 1 PD). After 4 cycles, the ORR was 73.1% (19/26, 11 CR, 8 PR, 4 SD, and 3 PD). After WBRT, the ORR was 90.9% (10/11, 7 CR, 3 PR, and 1 SD). The grade III and IV toxicity responses were mainly leukopenia (20.0%), thrombocytopenia (23.3%), and anemia (10.0%).
Fotemustine-based therapy in combination with rituximab chemotherapy followed by WBRT can improve outcomes, providing ORR benefits and favorable tolerability in patients newly diagnosed with PCNSL.
Although fruits and vegetable consumption has been shown to be associated with lower risks of mortality, cancers, and cardiovascular disease (CVD), there are limited data from China on the shape of ...the association. This study aimed to quantify the relationship between levels of fruit, vegetable, and legume consumption with the risk of major CVD, CVD mortality, cancer incidence, cancer mortality, and all-cause mortality.
In the baseline survey, participants attended 1 of 115 (45 urban and 70 rural) communities from 12 provinces to complete a standardized questionnaire, and undergo a physical examination between 2005 and 2009, and were followed up till 2017 (for the current analysis). Diet was assessed through in-person interviews by using validated food-frequency questionnaires. The clinical outcomes were adjudicated centrally by trained physicians using standardized definitions. Cox frailty models were used to explore the associations between fruit, vegetable, and legume consumption with the risk of all-cause, CVD, and cancer mortality.
A total of 41 243 participants were eligible for inclusion in the analyses. The average combined average daily intake of fruit, vegetable, and legume was 2.97 standard deviation (SD) 1.22 servings per day. During a median follow-up of 8.9 years interquartile range (IQR) 6.7–9.9 years, we recorded 1893 major CVDs, 794 cancer events, and 1324 deaths, with 411 CVD deaths and 429 cancer deaths. In the models adjusted for age, sex, and center (random effect), a higher total intake of fruit, vegetable, and legume was inversely associated with CVD mortality, cancer incidence, cancer mortality, and all-cause mortality. After adjusting for additional covariates, the associations were evidently attenuated and only the association with all-cause mortality (hazard ratio HR trend 0.92, 95% CI 0.86–0.98, p trend = 0.021) remained significant, with a non-significant trend for major CVD (HR trend 1.02, 95% CI 0.97–1.08, p trend = 0.449), CVD mortality (HR trend 0.94, 95% CI 0.84–1.06, p trend = 0.301), cancer incidence (HR trend 0.97, 95% CI 0.89–1.06, p trend = 0.540), or cancer mortality (HR trend 0.92, 95% CI 0.82–1.04, p trend = 0.174). Compared with the reference group, the risk of all-cause mortality was the lowest for four to five servings of total daily intake of fruit, vegetable, and legume (HR 0.73, 95% CI 0.55–0.97), and did not show a further decrease for the higher intake group. Separately, fruit intake was associated with a lower risk of all-cause mortality (HR trend 0.92, 95% CI 0.86–0.99, p trend = 0.020) and legume intake was associated with a lower risk of major CVD (HR trend 0.95, 95% CI 0.90–0.99, p trend = 0.028) and all-cause mortality (HR trend 0.94, 95% CI 0.89–0.99, p trend = 0.020) in the fully adjusted models.
This prospective study suggests that Chinese people with daily consumption of four to five servings (equivalent to 500–625 g/day) of fruit, vegetable, and legume demonstrated the lowest mortality, which conveys an encouraging message to the public that lifestyle modification to increase fruit, vegetable, and legume intakes may have greater beneficial effects on reducing all-cause mortality.
This study investigated the effects of dexmedetomidine on cardiovascular response during the decannulation period of general anesthesia in patients with different genotypes of angiotensin-converting ...enzyme (ACE) and essential hypertension.
The present study enrolled patients with essential hypertension and American Society of Anesthesiologists class II or III who were scheduled to undergo abdominal surgery under general anesthesia. Patients were assigned to 1 of 6 groups according to ACE genotype, as detected by polymerase chain reaction–restriction fragment length polymorphism, as follows: DD; ID; II; and DD, ID, and II each with dexmedetomidine (Dex). Dexmedetomidine was intravenously infused at 0.5 μg/kg/h for 30 min before the end of surgery in groups DD (Dex), ID (Dex), and II(Dex). Anesthesia was induced and maintained by the same anesthetics in all patients. Systolic and diastolic blood pressure, heart rate (HR), ECG, and rate-pressure product were recorded before anesthesia induction; at 30 min before the end of surgery; at the end of surgery; and at 0, 1.5, 5, and 10 min after extubation.
A total of 210 patients were enrolled (n = 35 per genotype). After extubation, systolic and diastolic blood pressure, HR, and RPP were increased markedly from baseline in groups DD, ID, and II; the increases were greater in groups DD and ID than in group II. No significant changes in blood pressure, HR, or RPP were found, and proper sedative was achieved in groups DD (Dex), ID (Dex), and II(Dex). The prevalences of cardiac arrhythmia were higher in groups DD and ID than in groups II, DD (Dex), ID (Dex), and II(Dex).
Patients essential hypertension and the ACE D allele had a strong hemodynamic response to tracheal extubation, on which dexmedetomidine was found to have both a prevention and treatment effect
Background: Mitochondrial calcium uniporter regulator 1 (MCUR1, also known as CCDC90A) is a protein-coding gene that plays a key role in mitochondrial calcium uptake. However, knowledge about its ...clinical significance in breast cancer is still limited. Methods: The expression profile of MCUR1 in various cancers was analyzed via the ONCOMINE and Tumor Immune Estimation Resource databases. The correlation between MCUR1 expression and the clinical features of breast cancer was investigated using UALCAN and MEXPRESS. Immunohistochemical analysis was applied to verify the expression of MCUR1 in breast cancer. The prognostic significance of MCUR1 in breast cancer was evaluated using Kaplan-Meier plotter and the PrognoScan database. Gene Set Enrichment Analysis (GSEA) was performed to explore the possible biological functions of MCUR1. In addition, the function of MCUR1 was examined by gene silencing in vitro. Western blotting was applied to detect the expression of proteins. Results: MCUR1 was overexpressed in breast cancer and significantly related to the clinical characteristics of breast cancer. Results from the public databases and IHC analysis indicated that MCUR1 expression was the highest in triple-negative breast cancer (TNBC). The high expression of MCUR1 was associated with poor overall survival, distant metastasis-free survival, and recurrence-free survival. GSEA showed that the hypoxia pathway, cellular reactive oxygen species (ROS) pathway, epithelial-mesenchymal transition pathway, and notch signaling pathway were differentially enriched in the high MCUR1 expression phenotype. In vitro experiments showed that MCUR1 knockdown in TNBC cell lines led to a decrease in cellular ROS and weakened cell migration and invasion abilities. Moreover, Western blotting showed that MCUR1 knockdown inhibited the epithelial- mesenchymal transition of TNBC cells via the ROS/Nrf2/Notch pathways. Conclusion: Our study suggests that MCUR1 plays a pivotal role in the malignant progression of breast cancer. Keywords: MCUR1, breast cancer, reactive oxygen species, epithelial-mesenchymal transition
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