Kefir peptides mitigate bleomycin-induced pulmonary fibrosis in mice through modulating oxidative stress, inflammation and gut microbiota.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and life-threatening lung disease with high mortality rates. The limited availability of effective drugs for IPF treatment, coupled with concerns regarding adverse effects and restricted responsiveness, underscores the need for alternative approaches. Kefir peptides (KPs) have demonstrated antioxidative, anti-inflammatory, and antifibrotic properties, along with the capability to modulate gut microbiota. This study aims to investigate the impact of KPs on bleomycin-induced pulmonary fibrosis. METHODS: Mice were treated with KPs for four days, followed by intratracheal injection of bleomycin for 21 days. Comprehensive assessments included pulmonary functional tests, micro-computed tomography (µ-CT), in vivo image analysis using MMPsense750, evaluation of inflammation- and fibrosis-related gene expression in lung tissue, and histopathological examinations. Furthermore, a detailed investigation of the gut microbiota community was performed using full-length 16 S rRNA sequencing in control mice, bleomycin-induced fibrotic mice, and KPs-pretreated fibrotic mice. RESULTS: In KPs-pretreated bleomycin-induced lung fibrotic mice, notable outcomes included the absence of significant bodyweight loss, enhanced pulmonary functions, restored lung tissue architecture, and diminished thickening of inter-alveolar septa, as elucidated by morphological and histopathological analyses. Concurrently, a reduction in the expression levels of oxidative biomarkers, inflammatory factors, and fibrotic indicators was observed. Moreover, 16 S rRNA sequencing demonstrated that KPs pretreatment induced alterations in the relative abundances of gut microbiota, notably affecting Barnesiella_intestinihominis, Kineothrix_alysoides, and Clostridium_viride. CONCLUSIONS: Kefir peptides exerted preventive effects, protecting mice against bleomycin-induced lung oxidative stress, inflammation, and fibrosis. These effects are likely linked to modifications in the gut microbiota community. The findings highlight the therapeutic potential of KPs in mitigating pulmonary fibrosis and advocate for additional exploration in clinical settings.

Aldo-keto reductase family 1 member A1 (AKR1A1) exerts a protective function in alcohol-associated liver disease by reducing 4-HNE accumulation and p53 activation.

BACKGROUND: The development of alcohol-associated liver disease (ALD) is influenced by the amount and duration of alcohol consumption. The resulting liver damage can range from reversible stages, such as steatosis, steatohepatitis and alcoholic fibrosis, to the advanced and irreversible stage of cirrhosis. Aldo-keto reductase family 1 member A1 (AKR1A1) is a member of the aldo-keto reductase family that catalyzes the reduction of aldehyde groups to their corresponding alcohols in an NADPH-dependent manner. AKR1A1 was found to be downregulated in patients diagnosed with ALD. This study aims to interpret the protective effects of AKR1A1 on the development of ALD. METHODS: A 5% alcohol-fed (AF) Akr1a1 knockout (Akr1a1-/-) mouse model and an AML12 hepatocyte model were used. The effects of AKR1A1 on liver function, inflammation, oxidative stress, lipid accumulation, and fibrosis were assessed by ELISA, western blotting, RT‒PCR, and a variety of histological staining methods in AF-induced wild-type (WT) and Akr1a1-/- mice compared to control liquid diet-fed (PF) WT and Akr1a1-/- mice. RESULTS: The results demonstrated that AF-WT mice expressed higher levels of AKR1A1 than WT mice fed a control diet, and they did not show any noticeable liver steatosis. However, AF-Akr1a1-/- mice displayed a lower survival rate and more severe liver injury than AF-WT mice, as demonstrated by increased proinflammatory cytokines, oxidative stress, lipid accumulation, fibrosis, and reduced antioxidant enzymes in their livers. Additionally, elevated levels of 4-HNE and p53 phosphorylation were observed in AF-Akr1a1-/- mice, suggesting that the loss of AKR1A1 led to increased 4-HNE accumulation and subsequent activation of p53, which contributed to the progression of ALD. Furthermore, in AML12 hepatocytes, Akr1a1 knockdown aggravated oxidative stress and steatosis induced by palmitic acid/oleic acid (P/O) inflammation induced by lipopolysaccharide (LPS), and fibrosis induced by TGF-ß1. CONCLUSIONS: This loss-of-function study suggests that AKR1A1 plays a liver-protective role during chronic alcohol consumption by reducing the accumulation of 4-HNE and inhibiting 4-HNE-mediated p53 activation.

A case report on multiple acyl-CoA dehydrogenase deficiency with severe myopathy and osteoporosis.

A 35-year-old male patient presented fluctuating bilateral lower extremity weakness for 3 years. Physical examination showed grade 4 proximal muscle weakness in both lower extremities and grade 5 distal muscle weakness. Laboratory data revealed elevated creatine kinase, triglycerides, and cholesterol. Muscle pathology showed deposition of lipid droplet under the sarcolemma. Bone densitometry indicated severe osteoporosis. Next-generation sequencing revealed a pathogenic mutation in the ETFDH gene. The patient was diagnosed with late-onset multiple acyl-CoA dehydrogenase deficiency. After riboflavin treatment, symptoms of the patient were relieved, physical endurance was restored, and bone mineral density was improved.

The rocker-soled shoes change the kinematics and muscle contractions of the lower extremity during various functional movement.

While rocker-shaped soles have become popular for running shoes, whether or not this type of shoe benefits other functional movements has rarely been discussed. The purpose of this study was to investigate the effect of rocker-soled shoes on lower extremity biomechanics during different exercises. Seventeen healthy university students were recruited. A motion capture analysis system and surface electromyography were used to measure kinematics and muscle activation while walking (10 m), running (10 m), cutting, jumping, and ascending and descending stairs. The results showed that when wearing rocker-soled shoes, greater peak external ankle rotation was present during most exercises. Smaller peak joint angles were observed in hip extension and external rotation when walking, and in ankle dorsiflexion when ascending stairs and jumping. The vastus medialis and vastus lateralis contracted more in most exercises when rocker-soled shoes were worn. However, the biceps femoris and medial gastrocnemius showed less muscle contraction. Wearing rocker-soled shoes during testing movements change the kinematics and muscle contractions of the lower extremity. These findings may provide information for choosing shoes for different exercises or training purposes.

Efficient quantum memory for photonic polarization qubits generated by cavity-enhanced spontaneous parametric downconversion.

Quantum memories, for storing then retrieving photonic quantum states on demand, are crucial components for scalable quantum technologies. Spontaneous parametric downconversion (SPDC) with a nonlinear crystal is the most widely used process for generating entangled photon pairs or heralded single photons. Despite the desirability of efficient quantum memories for SPDC-generated single photons, the storage and retrieval efficiencies achieved with this approach still fall below 50%, a threshold value for practical applications. Here, we report an efficiency of > 70% for the storage of heralded single photons generated by cavity-enhanced SPDC using atomic quantum memories based on electromagnetically induced transparency (EIT). In addition, we demonstrate the quantum memory for single-photon polarization qubits with a fidelity of ∼96%. This result paves the way towards the development of large-scale quantum networks.

Vascular Trauma in the Extremities: Factors Associated with the Outcome and Assessment of Amputation Indexes.

Background: Traumatic vascular injury in the extremities may be associated with a low mortality rate but can lead to limb loss that seriously affects patients' functionality. Multiple scoring systems have been designed to evaluate the prognosis, but none are 100% predictive. The management of traumatic vascular injury remains challenging and depends mostly on the surgeon's experience. Objectives: We identified the risks associated with limb loss and further investigated the utility of current amputation indexes. Methods: We retrospectively reviewed 53 cases of traumatic vascular injury in the extremities at a tertiary referral medical center over the past ten years (January 2011-December 2020). The mangled extremity severity score (MESS), limb salvage index (LSI), and predictive salvage index (PSI) were used to assess the traumatized limbs. The injury characteristics and outcomes were evaluated using regression analysis. Results: The incidence of limb loss was 20.8% (n = 11), and open fractures were the most related factor. Extensive involvement of soft tissue, vascular injury combined with tibia or fibula fractures, initial shock status, and the amount of transfusion were associated with limb loss. Conclusions: Our study identified the risk factors and clinical utility of MESS, PSI, and LSI. While both LSI and PSI had acceptable diagnostic accuracy, amputation should be decided based on a variety of criteria and clinical features. Salvaging any limb that has not become apparently futile seems logical, yet the presence of certain factors may suggest a worse outcome.

Human amniotic fluid mesenchymal stem cells attenuate pancreatic cancer cell proliferation and tumor growth in an orthotopic xenograft mouse model.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a malignant cancer and chemotherapy ineffectively treats PDAC, leading to the requirement for alternative tumor-targeted treatment. Human amniotic fluid mesenchymal stem cells (hAFMSCs) have been revealed to suppress tumor growth in various cancers and they are a strong candidate for treating PDAC. METHODS: To evaluate the effects of hAFMSCs on human pancreatic carcinoma cells (PANC1, AsPC1 and BxPC3 cell lines) and the possible mechanism involved, an in vitro cell coculture system was used. A PANC1 orthotopic xenograft mouse model was established and hAFMSCs were injected intravenously at 4 weeks post-xenograft. RESULTS: An in vitro coculture assay showed that hAFMSCs inhibited PANC1 cell proliferation by inducing S phase cell cycle arrest and increased cell apoptosis in a time-dependent manner. In PANC1 cells, hAFMSCs caused the downregulation of Cyclin A and Cyclin B1 as well as the upregulation of p21 (CDKN1A) at 24 h post coculture. The upregulation of pro-apoptotic factors Caspase-3/-8 and Bax at 24 h post coculture reduced the migration and invasion ability of PANC1 cells through inhibiting the epithelial-mesenchymal transition (EMT) process. In a PANC1 orthotopic xenograft mouse model, a single injection of hAFMSCs showed significant tumor growth inhibition with evidence of the modulation of cell cycle and pro-apoptotic regulatory genes and various genes involved in matrix metallopeptidase 7 (MMP7) signaling-triggered EMT process. Histopathological staining showed lower Ki67 levels in tumors from hAFMSCs-treated mice. CONCLUSIONS: Our data demonstrated that hAFMSCs strongly inhibit PDAC cell proliferation, tumor growth and invasion, possibly by altering cell cycle arrest and MMP7 signaling-triggered EMT.

Successful Surgical Salvage for a Patient with Ruptured Coronary Sinus during Percutaneous Ablation for Atrial Fibrillation: A Case Report.

Herein, we describe the rare anatomy of an abnormal shunt from the left atrium to the coronary sinus, which ruptured during a percutaneous ablation for atrial fibrillation. The iatrogenic lesion was successfully repaired after emergent extracorporeal membrane oxygenation set up followed by surgical exploration. The patient's postoperative course was uneventful, and she was regularly followed up without any complications.

Deep Venous Thrombosis and Risk of Consequent Sepsis Event: A Retrospective Nationwide Population-Based Cohort Study.

Deep vein thrombosis causes several acute and chronic vessel complications and puts patients at risk of subsequent sepsis development. This unique study aimed to estimate the risk of sepsis development in DVT patients compared with non-DVT patients. This population-based cohort study used records of a longitudinal health insurance database containing two million patients defined in Taiwan's National Health Insurance Research Database (NHIRD). Our study included patients aged over 20 years with a new diagnosis of DVT with at least two outpatient department visits or an admission between 2001 and 2014. Patients with a diagnosis of sepsis before the index date were excluded. Propensity score matching (PSM) was used to homogenize the baseline characteristics between the two groups. To define the independent risk of the DVT group, a multivariate Cox proportional hazard model was used to estimate the hazard ratios. After PSM, the DVT group (n = 5753) exhibited a higher risk of sepsis (adjusted hazard ratio, aHR, 1.74; 95% CI, 1.59-1.90) compared with non-DVT group (n = 5753). Patients with an increased risk of sepsis were associated with being elderly aged, male, having diabetes, chronic kidney disease, chronic obstructive pulmonary disease, stroke, malignancy, and use of antibiotics. In conclusion, this population-based cohort study demonstrated an increased risk of sepsis in DVT patients compared with non-DVT patients. Thus, early prevention and adequate treatment of DVT is necessary in clinical practice.

Additive Antiproliferative and Antiangiogenic Effects of Metformin and Pemetrexed in a Non-Small-Cell Lung Cancer Xenograft Model.

Lung cancer is heterogeneous and challenging to cope with once it has progressed. Chemotherapy is the first step once no active driver mutation has been discovered. Non-antitumor drugs have been found to be beneficial when used as adjuvants to chemotherapy. In this study, the additive effect and mechanism of metformin combined with pemetrexed in non-small-cell lung cancer (NSCLC) cells were elucidated. Three NSCLC cell lines, A549, H1975, and HCC827, were used to analyze tumor cell proliferation, colony formation and the cell cycle in vitro when exposed to metformin alone, pemetrexed alone or their combination. We found that combination treatment in three cell lines exerted antiproliferative effects through cell cycle arrest in the S phase. An ex vivo chicken chorioallantoic membrane (CAM) assay was used to examine the antiangiogenic effect of metformin combined with pemetrexed on vascular structure formation. We further created an A549 orthotopic xenograft model with an in vivo imaging system (IVIS) and explored the associated indicators involved in the tumorigenic process. The in vitro results showed that the combination of metformin and pemetrexed exhibited an antiproliferative effect in reducing cell viability and colony formation, the downregulation of cyclin D1 and A2 and the upregulation of CDKN1B, which are involved in the G1/S phase. For antiangiogenic effects, the combination therapy inhibited the vascular structure, as proven by the CAM assay. We elucidated that combination therapy could target VEGFA and Endoglin by RT-qPCR, ELISA and histopathological findings in an A549 orthotopic NSCLC xenograft model. Our research demonstrated the additive antiproliferative and antiangiogenic effects of the combination of metformin with pemetrexed in NSCLC and could be applied to clinical lung cancer therapy.

Risk of Mortality and Readmission among Patients with Pelvic Fracture and Urinary Tract Infection: A Population-Based Cohort Study.

Patients with pelvic fractures could encounter various complications during or after treatments. This cohort study investigated the risk of mortality and readmissions in patients with pelvic fractures, with or without urinary tract infections (UTIs), within 30 days following the pelvic fractures. This retrospective cohort study examined claim records from the Longitudinal Health Insurance Database 2000 (LHID2000). We selected patients hospitalized with pelvic fractures between 1997 and 2013 for study. Patients who had index data before 2000 or after 2010 (n = 963), who died before the index date (n = 64), who were aged <18 years (n = 94), or who had a pelvic injury (n = 31) were excluded. In total, the study cohort comprised 1623 adult patients; 115 had UTIs, and 1508 patients without UTIs were used as a comparison cohort. Multivariate analysis with a multiple Cox regression model and Kaplan-Meier survival analysis were performed to analyze the data. Our results showed that the 1-year mortality rate (adjusted hazard ratio [HR]: 2.32; 95% CI: 1.25-4.29) and readmission rate (adjusted HR: 1.72; 95% CI: 1.26-3.34) of the UTI group were significantly higher than those of the non-UTI group. Moreover, the Kaplan-Meier curve for the 1-year follow-up indicated that the UTI group had a higher cumulative risk of both mortality and hospital readmission compared with the non-UTI group. In conclusion, among patients with pelvic fracture, patients with UTI were associated with increased risks of mortality and readmission. Physicians must pay more attention to such patients to prevent UTIs among patients with pelvic fractures during hospitalization and conduct a follow-up after discharge within at least 1 year.

Association Between Aspirin Use and Decreased Risk of Pneumonia in Patients With Cardio-Cerebra-Vascular Ischemic Disease: A Population-Based Cohort Study.

This study evaluated the association between long-term low-dose aspirin use and decreased risk of pneumonia in patients with cardio-cerebra-vascular ischemic diseases (CCVDs). This retrospective cohort study used records from Taiwan's National Health Insurance Research Database of claims made between 1997 and 2013. After propensity score matching (PSM), patients who took a low dose of aspirin for more than 90 days within 1 year of diagnosis with CCVDs were identified as the exposure group (n = 15,784). A matched total of 15,784 individuals without aspirin use were selected for the non-aspirin group. The main outcome was the development of pneumonia after the index date. Multivariable Cox regression analysis and Kaplan-Meier survival analysis were performed to estimate the adjusted hazard ratio (aHR) and cumulative probability of pneumonia. The result after PSM indicated a lower hazard ratio for pneumonia in aspirin users (aHR = 0.890, 95% confidence interval = 0.837-0.945). Therefore, patients with CCVDs who took aspirin had a lower risk of developing pneumonia than those who did not. In conclusion, this population-based cohort study demonstrated that long-term low-dose aspirin use is associated with a slightly decreased risk of pneumonia in patients with CCVDs.

Risk of Pneumonia in Pediatric Patients Following Minor Chest Trauma: A Population-Based Retrospective Cohort Study.

This study investigated the association between minor chest trauma and the risk of pneumonia among pediatric patients in a Taiwanese health care setting. For this retrospective population-based cohort study, the Longitudinal Health Insurance Database was used to analyze the data of patients with a minor chest injury between 2010 and 2012. Data were analyzed through a multivariate analysis with a multiple Cox regression model. Patients were divided into a chest trauma group (n = 6592) and a non-chest trauma group (n = 882,623). An increased risk of pneumonia was observed in the chest trauma group (hazard ratio = 1.23; 95% confidence interval = 1.02-1.49) compared to the non-chest trauma group. In conclusion, this population-based cohort study demonstrated that pediatric patients with minor chest trauma are at an increased risk of pneumonia. The short-term adverse effects of pneumonia could be severe when a patient suffers from mild chest trauma.

Generation of sub-MHz and spectrally-bright biphotons from hot atomic vapors with a phase mismatch-free scheme.

We utilized the all-copropagating scheme, which maintains the phase-match condition, in the spontaneous four-wave mixing (SFWM) process to generate biphotons from a hot atomic vapor. The linewidth and spectral brightness of our biphotons surpass those of the biphotons produced with the hot-atom SFWM in the previous works. Moreover, the generation rate of the sub-MHz biphoton source in this work can also compete with those of the sub-MHz biphoton sources of the cold-atom SFWM or cavity-assisted spontaneous parametric down conversion. Here, the biphoton linewidth is tunable for an order of magnitude. As we tuned the linewidth to 610 kHz, the generation rate per linewidth is 1,500 pairs/(s·MHz) and the maximum two-photon correlation function, gs,as(2), of the biphotons is 42. This gs,as(2) violates the Cauchy-Schwarz inequality for classical light by 440 folds, and demonstrates that the biphotons have a high purity. By increasing the pump power by 16 folds, we further enhanced the generation rate per linewidth to 2.3×104 pairs/(s·MHz), while the maximum gs,as(2) became 6.7. In addition, we are able to tune the linewidth down to 290±20 kHz. This is the narrowest linewidth to date among all single-mode biphoton sources of room-temperature and hot media.

Efficient frequency conversion based on resonant four-wave mixing.

Efficient frequency conversion of photons has important applications in optical quantum technology because the frequency range suitable for photon manipulation and communication usually varies widely. Recently, an efficient frequency conversion system using a double-Λ four-wave mixing (FWM) process based on electromagnetically induced transparency (EIT) has attracted considerable attention because of its potential to achieve a nearly 100% conversion efficiency (CE). To obtain such a high CE, the spontaneous emission loss in this resonant-type FWM system must be suppressed considerably. A simple solution is to arrange the applied laser fields in a backward configuration. However, the phase mismatch due to this configuration can cause a significant decrease in CE. Here, we demonstrate that the phase mismatch can be effectively compensated by introducing the phase shift obtained by two-photon detuning. Under optimal conditions, we observe a wavelength conversion from 780 to 795 nm with a maximum CE of 91.2%±0.6% by using this backward FWM system at an optical depth of 130 in cold 87Rb atoms. The current work represents an important step toward achieving low-loss, high-fidelity quantum frequency conversion based on EIT.

Exploring Potential Proteomic Biomarkers for Prognosis of Infective Endocarditis through Profiled Autoantibodies by an Immunomics Protein Array Technique.

Though infective endocarditis (IE) is a life-threatening cardiac infection with a high mortality rate, the effective diagnostic and prognostic biomarkers for IE are still lacking. The aim of this study was to explore the potential applicable proteomic biomarkers for IE through the Immunome™ Protein Array system. The system was employed to profile those autoantibodies in IE patients and control subjects. Our results showed that interleukin-1 alpha (IL1A), nucleolar protein 4 (NOL4), tudor and KH domain-containing protein (TDRKH), G antigen 2B/2C (GAGE2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and X antigen family member 2 (XAGE2) are highly differentially-expressed among IE and non-IE control. Furthermore, bactericidal permeability-increasing protein (BPI), drebrin-like protein (DBNL), signal transducing adapter molecule 2 (STAM2), cyclin-dependent kinase 16 (CDK16), BAG family molecular chaperone regulator 4 (BAG4), and nuclear receptor-interacting protein 3 (NRIP3) are differentially-expressed among IE and healthy controls. On the other hand, those previously identified biomarkers for IE, including erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, procalcitonin, and N-terminal-pro-B-type natriuretic peptide demonstrated only minor significance. With scientific rationalities for those highly differentially-expressed proteins, they could serve as potential candidates for diagnostic biomarkers of IE for further analysis.