Extremity injuries resulting from motor vehicle collisions, especially those leading to bone-exposed wounds, present challenges for achieving effective wound coverage. Such injuries are susceptible ...to complications including infections, osteomyelitis, and unexpected amputations due to inadequate blood supply. Severe traumatic degloving injuries often entail damage to the surrounding blood vessels, making local or free flaps impractical choices in many cases. Consequently, treatment options may vary based on distinct clinical scenarios, with no standardized guidelines available. Our study introduces an integrated approach utilizing dermal substitutes and skin grafts as a safer treatment modality for managing large-area tibial exposure resulting from traffic accidents.
A 66-year-old male with a compromised nutritional status was struck by a car while riding a motorcycle. Previous attempts using double-layer Integra and negative pressure wound therapy (NPWT) for two-stage reconstruction have been unsuccessful.
Computed tomography imaging studies revealed multiple comminuted and displaced fractures involving the left femoral shaft, left proximal tibia, left patella, and proximal fibula, as well as a fracture of the right fibular shaft and an avulsion fracture of the right distal medial femur. The patient's condition corresponded to Type 3B in the Gustilo classification for open fractures, and the patient had an Injury Severity Score of 25.
We applied a one-stage reconstruction involving single-layer Integra, split-thickness skin grafts, NPWT, and nutritional supplements containing various amino acids.
By implementing an integrated treatment approach and providing diligent wound care over a total of 2 months, the patient achieved successful healing and expressed satisfaction with the postoperative results.
This study offers insights into the effectiveness of employing one-stage reconstruction for traumatic injuries with extensive exposed tibias. In addition, it underscores the impact of a patient's nutritional status on wound healing and introduces a potential solution for similar challenging cases.
Oral cancer is a subtype of head and neck cancer which represents 2.65% of all human malignancies. Most of oral cancer is histopathologically diagnosed as oral squamous cell carcinoma (OSCC). OSCC is ...characterized by a high degree of local invasion and a high rate of metastasis to the cervical lymph nodes. How to prevention and treatment of OSCC is important and imperative. Here, we investigated the therapeutic effect and molecular mechanism of cantharidin, an active compound isolated from blister beetles, on OSCC in vitro. Results showed that cantharidin significantly decreased cell viability in human tongue squamous carcinoma-derived SAS, CAL-27, and SCC-4 cell lines. The further mechanistic studies were carried out in SAS cells. Cantharidin also significantly increased apoptosis-related signals, including caspase-9, caspase-7 and caspase-3 proteins. Besides, cantharidin decreased mitochondrial transmembrane potential (MMP) and induced cytochrome c and apoptosis inducing factor (AIF) release. Cantharidin also increased Bax, Bid, and Bak protein expressions and decreased Bcl-2 protein expression. Cantharidin could also increase the endoplasmic reticulum (ER) stress signals, including the expressions of phosphorylated eIF-2α and CHOP, but not Grp78 and Grp94. Furthermore, cantharidin reduced pro-caspase-12 protein expression. In signals of mitogen-activated protein kinases, cantharidin increased the phosphorylation of JNK, but not ERK and p38. Transfection of shRNA-JNK to OSCC cells effectively reversed the cantharidin-induced cell apoptotic signals, including the mitochondrial and ER stress-related signaling molecules. Taken together, these findings suggest that cantharidin induces apoptosis in OSCC cells via the JNK-regulated mitochondria and ER stress-related signaling pathways.
Soluble epoxide hydrolase (sEH) is a bifunctional enzyme with COOH-terminal hydrolase and NH2-terminal lipid phosphatase activities. It is expressed in various cell types in the brain and is involved ...in the pathogenesis of inflammatory and neurodegenerative diseases. Alzheimer's disease (AD) is a progressive neuroinflammatory and neurodegenerative disease. However, the pathological significance of sEH and underlying molecular mechanism in AD remain unclear.
To examine the role of sEH in pathogenesis of AD, we used wild-type (WT) mice, soluble epoxide hydrolase deficient (sEH
) and two mouse models of AD, including amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic (APP/PS1 Tg) and APP/PS1 Tg/sEH
mice. Western blotting analysis and immunohistochemistry assay were performed to evaluate the protein expression. Locomotion, nesting building ability, Y-maze, and Morris water maze tests were conducted to study mouse behavior. The levels of interleukin (IL)-1β, IL-4, IL-6, and IL-10 and the activities of NF-κB and nuclear factor of activated T cells (NFAT) were measured by commercial assay kits. The quantitative protein level profiling in the brain lysate was analyzed using LC-MS/MS approaches.
We demonstrated that the level of sEH was increased in the brain and predominantly appeared in hippocampal astrocytes of APP/PS1 Tg mice. Genetic ablation of sEH in APP/PS1 Tg mice delayed the progression of AD as evidenced by the alleviation in behavior outcomes and Aβ plaque deposition. In addition, loss of the function of sEH in APP/PS1 Tg mice increased astrogliosis and the production of astrocyte-derived anti-inflammatory cytokines including IL-1β, IL-4, and IL-10, as well as the activity of NF-kB and NFAT. Moreover, analysis of gene ontology in the AD brain revealed that important signaling pathways and processes related to AD pathogenesis such as translational regulation, oxidative stress, cytoskeleton reorganization, and small GTPase signal transduction were altered in APP/PS1 Tg/sEH
mice compared with APP/PS1 Tg mice.
Our results suggest that sEH is a crucial regulator in the progression of AD and might be a potential therapeutic target for the treatment of AD.
Alcohol use disorder (AUD) is a spectrum of high risk behaviors including alcohol abuse and dependence. Chronic kidney disease (CKD) is progressive loss of renal function for more or equal to 3 ...months or presence of any irreversible kidney damage. Common risk factors of CKD have been identified, but the impact of alcohol consumption on kidney function is controversial. The study aims to investigate the relationship between alcohol use disorder and CKD on a national scale.
This retrospective cohort study was conducted using Taiwan's National Health Insurance research database. Patients aged 20 years or older, without CKD and with the diagnosis of AUD (ICD-9-CM codes 303.X; 305.0, V113) from years 2000 to 2013 were enrolled. Control cohort was selected to match the demographics of the target population. Patients were followed until the end of 2013 or earlier if they developed CKD, died, or lost follow up. Baseline characteristics and comorbidities were identified for risk stratification.
We identified 11639 patients in the AUD cohort and 46556 patients in the control cohort. Compared to patients in the control cohort, those in the AUD group were more likely to have multiple comorbidities (p < 0.001 for all comorbidities). After adjustment of age, gender, baseline comorbidities, and nonsteroidal anti-inflammatory drug use, the diagnosis of AUD was associated with an increased risk of CKD development (aHR = 1.62, 95% CI, 1.46-1.81). During the mean follow up periods of 6.47 (standard deviation (SD) = 3.80) years for the AUD cohort and 7.23 (SD = 3.75) years for the control cohort, the overall incidence density of CKD was significantly higher in patients with AUD than those in the control cohort (3.48 vs 6.51 per 1000 person-years, aHR = 1.68, 95% CI, 1.50-1.87). Kaplan-Meier analysis showed that the AUD cohort had a higher cumulative incidence of CKD than the control cohort (log-rank test, p value < 0.001). Patients with AUD had higher risks of CKD in all the stratified groups, except for the subgroup with age over 65 years old.
Our study suggested that AUD was associated with an increased incidence of newly diagnosed CKD by nearly two folds. Young age, in particular, had a higher association between AUD and CKD. Considering the preventable nature of AUD, establishing effective health policies is imperative to reduce high-risk alcohol behaviors and thereby prevent alcohol-related kidney disease. Further prospective studies are warranted to further elucidate the causation of AUD on kidney function.
Rationale: Reconstructive surgery is widely considered the primary treatment for soft tissue defects around the knee owing to its high flexibility. However, in our recent case study, we explored an ...alternative approach using decellularized collagen dressings, which proved highly effective in healing a soft tissue defect involving bone exposure following surgical correction of a traumatic patellar dislocation. Patient concerns: A 65-year-old male with a traumatic patellar dislocation in the lower extremity failed to approximate the wound after surgical correction. The patient refused additional surgical reconstruction because of the potential risks of multiple operative complications. Diagnoses: Traumatic patellar dislocation complicated by exposed bone following surgical treatment was made. Interventions: The procedure was performed using ABCcolla® Collagen Matrix (ACRO Biomedical, Taiwan), an acellular dermal matrix made from a decellularized native porcine collagen scaffold dressing. Collagen dressings were applied to the soft tissue defect, and biointegration was observed in the wound area of bone exposure. Outcomes: Through the application of ABCcolla® Collagen Matrix (ACRO Biomedical, Taiwan) and diligent wound care for a total of 105 days, the patient healed successfully and achieved partial functional recovery after undergoing rehabilitation. During recent outpatient clinic visits, the patient is now able to ambulate independently with the aid of crutches. Lessons: Collagen dressings circumvent the potential risks and complications associated with multiple surgical procedures. We believe that the utilization of collagen dressings, combined with careful wound management, could serve as a promising alternative treatment option for patients with soft tissue defects around the knee in the future.
Characterizing the mechanistic interactions between exposures and diseases is one of the most critical issues in epidemiologic studies. Previous studies have proposed a stochastic sufficient ...component cause framework, under which each sufficient cause is treated as a stochastic process instead of a time‐invariant random variable. However, different types of mechanistic interactions such as synergism and agonism cannot be further identified. In this study, we proposed a stochastic marginal sufficient component cause model to conceptualize and identify agonism and synergism by exploiting the additional information. We further provided six approaches to identify and estimate agonism and synergism based on an additive hazard model and a complementary log model. Researchers can easily adjust confounding factors by including appropriate covariates into a regression model. Simulations have proven that approaches under three models are all valid tests. The power of an additive hazard model increases as the total follow‐up time increases and is higher than that of the other two models. We applied this method to a Taiwanese cohort data set to investigate the mechanistic interaction among hepatitis B and C viruses on the incidence of hepatocellular carcinoma. The hazard of people with agonistic interaction is 1.28×10−5 (95% CI: 6.97×10−6, 1.87×10−5), and the cumulative hazard of those people is 7.41×10−2 (95% CI: 4.09×10−2, 1.07×10−1), which is approximately 3.5 times stronger than that of synergistic interaction. The proposed method makes it possible to quantify different types of mechanistic interactions in longitudinal studies with censored data.
•As3+ induced a concomitant activation of apoptosis and autophagy in neuronal cell death.•Akt inactivation-regulated autophagy was involved in As3+-induced neuronal apoptosis.•AMPK activation played ...an important role in the As3+-triggered neuronal cell autophagy contributing to apoptosis.
Inorganic arsenic (As3+), a well-known worldwide industrial and environmental pollutant, has been linked to neurodegenerative disorders (NDs). Autophagy plays an important role in controlling neuronal cell survival/death. However, limited information is available regarding the toxicological mechanism at the interplay between autophagy and As3+-induced neurotoxicity. The present study found that As3+ exposure induced a concomitant activation of apoptosis and autophagy in Neuro-2a cells, which was accompanied with the increase of phosphatidylserine exposure on outer membrane leaflets and apoptotic cell population, and the activation of caspase-3, -7, and PARP as well as the elevation of protein expressions of LC3-II, Atg-5, and Beclin-1, and the accumulation of autophagosome. Pretreatment of cells with autophagy inhibitor 3-MA, but not that of Z-VAD-FMK (a pan-caspase inhibitor), effectively prevented the As3+-induced autophagic and apoptotic responses, indicating that As3+-triggered autophagy was contributing to neuronal cell apoptosis. Furthermore, As3+ exposure evoked the dephosphorylation of Akt. Pretreatment with SC79, an Akt activator, could significantly attenuated As3+-induced Akt inactivation as well as autophagic and apoptotic events. Expectedly, inhibition of Akt signaling with LY294002 obviously enhanced As3+-triggered autophagy and apoptosis. Exposure to As3+ also dramatically increased the phosphorylation level of AMPKα. Pretreatment of AMPK inhibitor (Compound C) could markedly abrogate the As3+-induced phosphorylated AMPKα expression, and autophagy and apoptosis activation. Taken together, these results indicated that As3+ exerted its cytotoxicity in neuronal cells via the Akt inactivation/AMPK activation downstream-regulated autophagy-dependent apoptosis pathways, which ultimately lead to cell death. Our findings suggest that the regulation of Akt/AMPK signals may be a promising intervention to against As3+-induced neurotoxicity and NDs.
In our department, the levels of viral hepatitis markers, including hepatitis B surface antigen and hepatitis C antibodies, were measured, and the results were negative. ...significant jaundice was ...observed, with a total bilirubin level of 5.1 mg/dl (initially 1.9 mg/dl). ...we arranged a liver biopsy for evaluation. Only ~10% of AIH patients do not have any of these autoantibodies. 3 We did not detect any autoantibodies in the serum of our patient, and our patient exhibited a poor response to the standard PBC treatment. ...a liver biopsy was necessary to obtain a definite diagnosis, and we finally obtained the uncommon diagnosis of AIH-PBC overlap syndrome, which requires treatment with both ursodeoxycholic acid and steroids.
Mesenchymal stem cells (MSCs) are widely considered to be an attractive cell source for regenerative therapies, but maintaining multipotency and self-renewal in cultured MSCs is especially ...challenging. Hence, the development and mechanistic description of strategies that help promote multipotency in MSCs will be vital to future clinical use. Here, using an array of techniques and approaches, including cell biology, RT-quantitative PCR, immunoblotting, immunofluorescence, flow cytometry, and ChIP assays, we show that the extracellular domain of epithelial cell adhesion molecule (EpCAM) (EpEX) significantly increases the levels of pluripotency factors through a signaling cascade that includes epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3), and Lin-28 homolog A (LIN28) and enhances the proliferation of human bone marrow MSCs. Moreover, we found that EpEX-induced LIN28 expression reduces the expression of the microRNA LET7 and up-regulates that of the transcription factor high-mobility group AT-hook 2 (HMGA2), which activates the transcription of pluripotency factors. Surprisingly, we found that EpEX treatment also enhances osteogenesis of MSCs under differentiation conditions, as evidenced by increases in osteogenic markers, including Runt-related transcription factor 2 (RUNX2). Taken together, our results indicate that EpEX stimulates EGFR signaling and thereby context-dependently controls MSC states and activities, promoting cell proliferation and multipotency under maintenance conditions and osteogenesis under differentiation conditions.
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