Delayed neurological dysfunction following posterior laminectomy with lateral mass screw fixation: A case report and review of literature.

BACKGROUND: While most complications of cervical surgery are reversible, some, such as symptomatic postoperative spinal epidural hematoma (SEH), which generally occurs within 24 h, are associated with increased morbidity and mortality. Delayed neurological dysfunction is diagnosed in cases when symptoms present > 3 d postoperatively. Owing to its rarity, the risk factors for delayed neurological dysfunction are unclear. Consequently, this condition can result in irreversible neurological deficits and serious consequences. In this paper, we present a case of postoperative SEH that developed three days after hematoma evacuation. CASE SUMMARY: A 68-year-old man with an American Spinal Injury Association (ASIA) grade C injury was admitted to our hospital with neck pain and tetraplegia following a fall. The C3-C7 posterior laminectomy and the lateral mass screw fixation surgery were performed on the tenth day. Postoperatively, the patient showed no changes in muscle strength or ASIA grade. The patient experienced neck pain and subcutaneous swelling on the third day postoperatively, his muscle strength decreased, and his ASIA score was grade A. Magnetic resonance imaging showed hypointense signals on T1 weighted image (T1WI) and T2WI located behind the epidural space, with spinal cord compression. Emergency surgical intervention for the hematoma was performed 12 h after onset. Although hypoproteinemia and pleural effusion did not improve in the perioperative period, the patient recovered to ASIA grade C on day 30 after surgery, and was transferred to a functional rehabilitation exercise unit. CONCLUSION: This case shows that amelioration of low blood albumin and pleural effusion is an important aspect of the perioperative management of cervical surgery. Surgery to relieve the pressure on the spinal cord should be performed as soon as possible to decrease neurological disabilities.

Evaluating the Application Potential of a Recombinant Ganoderma Protein as Bioactive Ingredients in Cosmetics.

The aim of this study was to evaluate the application potential of a recombinant fungal immunomodulatory protein from Ganoderma lucidum (rFIP-glu). First, a recombinant plasmid pPIC9K::FIP-glu-His was transferred into Pichia pastoris for the production of protein. The protein was then to assess its free radical scavenging abilities and the effect on the viability of both human immortalized keratinocytes (HaCaT cells) and mouse B16-F10 melanoma cells (B16 cells) in vitro, followed by the effect on the melanin synthesis of B16 cells. The results of SDS-PAGE and western blot showed that rFIP-glu was successfully expressed. Furtherly, a bioactivity assay in vitro indicated that the scavenging rate of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals reached 84.5% at 6.0 mg/mL (p ≤ 0.0001) of rFIP-glu, showing strong antioxidant activity. Subsequently, a safety evaluation demonstrated that rFIP-glu promoted the proliferation of HaCaT cells, with the cell viability reaching 124.3% at 48 µg/mL (p ≤ 0.01), regarding the cell viability of B16 cells after exposure to rFIP-glu (48 µg/mL) significantly inhibited, to 80.7% (p ≤ 0.01). Besides, rFIP-glu inhibited the melanin synthesis of B16 cells in a dose-dependent manner from 100-1000 µg/mL, and rFIP-glu at 500 µg/mL (p ≤ 0.01) exhibited the highest intracellular melanin amount reduction of 16.8%. Furthermore, a mechanism analysis showed that rFIP-glu inhibited tyrosinase (TYR) activity by up-regulating the expression of the microphthalmia-associated transcription factor (MITF) and down-regulating the gene expression of TYR and tyrosinase-related protein-1 (TYRP-1), thus inhibiting melanin synthesis. The data implied that rFIP-glu had significant antioxidant activity and whitening potency. It should be used as raw materials for cosmeceutical applications.

Cardiovascular Toxicities of Ibrutinib: A Pharmacovigilance Study Based on the United States Food and Drug Administration Adverse Event Reporting System Database.

Background: Although ibrutinib has been widely used to treat haematological malignancies, many studies have reported associated cardiovascular events. These studies were primarily animal experiments and clinical trials. For more rational clinical drug use, a study based on post-marketing data is necessary. Aim: Based on post-marketing data, we investigated the clinical features, time to onset, and outcomes of potential cardiovascular toxicities of ibrutinib. Methods: This disproportionality study utilised data from the 2014−2021 United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. We used two disproportionality methods information component (IC) and reporting odds ratio (ROR)) to detect the potential cardiovascular toxicities of ibrutinib. Positive signals were defined as IC025 > 0 and ROR025 > 1. Results: A total of 10 cardiovascular events showed positive signals: supraventricular tachyarrhythmias, haemorrhagic central nervous system vascular conditions, ventricular tachyarrhythmias, cardiac failure, ischaemic central nervous system vascular conditions, cardiomyopathy, conduction defects, myocardial infarction, myocardial infarction disorders of sinus node function, and torsade de pointes/QT prolongation. Cardiomyopathy and supraventricular tachyarrhythmias were the two most common signals. Disorders of sinus node function were observed for the first time, which may be a new adverse effect of ibrutinib. Conclusions: This pharmacovigilance study systematically explored the adverse cardiovascular events of ibrutinib and provided new safety signals based on past safety information. Attention should be paid to some high-risk signals.

Toxicity signals associated with secukinumab: A pharmacovigilance study based on the United States Food and Drug Administration Adverse Event Reporting System database.

AIMS: Secukinumab, the first interleukin 17A inhibitor, is widely used to treat immune diseases, including plaque psoriasis, psoriatic arthritis and ankylosing spondylitis. Recently, many studies have reported adverse events associated with secukinumab, including gastrointestinal disorders, infections and infestations, and hypersensitive and nervous system disorders. OBJECTIVE: Here, we aimed to explore the clinical characteristics, outcomes and time to onset of the four main toxicities of secukinumab using post-marketing data. METHODS: Our study utilized data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2015 to 2021, using disproportionality analysis. Toxicities were defined based on the standardized Medical Dictionary for Regulatory Activities queries. Two disproportionality methods were used to detect potential signals: information component (IC) and reporting odds ratio (ROR). The signals were defined as ROR025 > 1 and IC025 > 0. RESULTS: A total of 73 945 398 records were included in this study, of which 300 665 records were related to secukinumab. Diarrhoea (N = 3538), nasopharyngitis (N = 3458), pruritus (N = 4277) and rash (N = 3270) were the most common adverse events. Inflammatory bowel disease (IC025 /ROR025 = 3.25/9.69), genital candidiasis (IC025 /ROR025 = 3.46/11.54), dermatitis psoriasiform (IC025 /ROR025 = 1.94/4.04) and anosmia (IC025 /ROR025 = 1.62/3.17) had the highest IC025 values of all toxicities. The time to onset of the four toxicities was mainly concentrated in the first month. Some patients simultaneously presented with two or more toxicities. CONCLUSION: This pharmacovigilance study systematically explored the four main toxicities of secukinumab and provided new safety signals based on past safety information. Some high-risk signals need to be given attention.

Chinese Cordyceps: Bioactive Components, Antitumor Effects and Underlying Mechanism-A Review.

Chinese Cordyceps is a valuable source of natural products with various therapeutic effects. It is rich in various active components, of which adenosine, cordycepin and polysaccharides have been confirmed with significant immunomodulatory and antitumor functions. However, the underlying antitumor mechanism remains poorly understood. In this review, we summarized and analyzed the chemical characteristics of the main components and their pharmacological effects and mechanism on immunomodulatory and antitumor functions. The analysis revealed that Chinese Cordyceps promotes immune cells' antitumor function by via upregulating immune responses and downregulating immunosuppression in the tumor microenvironment and resetting the immune cells' phenotype. Moreover, Chinese Cordyceps can inhibit the growth and metastasis of tumor cells by death (including apoptosis and autophagy) induction, cell-cycle arrest, and angiogenesis inhibition. Recent evidence has revealed that the signal pathways of mitogen-activated protein kinases (MAPKs), nuclear factor kappaB (NF-κB), cysteine-aspartic proteases (caspases) and serine/threonine kinase Akt were involved in the antitumor mechanisms. In conclusion, Chinese Cordyceps, one type of magic mushroom, can be potentially developed as immunomodulator and anticancer therapeutic agents.

Recent advances in bioactive peptides from cereal-derived Foodstuffs.

Cereal-derived proteins account for a major part of human dietary protein consumption. Natural bioactive peptides (NBPs) from these proteins involve a variety of physiological activities and play an important role in the promotion of human health. This review focuses on the characteristics of NBPs obtained from cereals, and the commonly used methods for preparation, separation, purification, and identification. We also discussed the biological functions of cereal-derived NBPs (CNBPs), including the activities of antioxidant, immunomodulatory, antimicrobial, and regulation of hyperglycaemia and hypertension. The paper summarised the latest progress in the research and application of CNBPs and analysed the prospects for the development and application of several protein by-products, providing an important way to improve the added value of protein by-products in cereal processing.

Updated Insights on Cardiac and Vascular Risks of Proton Pump Inhibitors: A Real-World Pharmacovigilance Study.

Background: Proton pump inhibitors (PPIs) are among the most widely prescribed medications in clinical practice. However, there are also concerns about the potential risks of long-term PPI use. The present study aimed to examine the safety of PPIs and summarize their potential cardiac and vascular risks in a real-world setting. Methods: This pharmacovigilance study extracted records between January 2015 and December 2019 from the FDA Adverse Event Reporting System (FAERS) database. The association of seven PPI medications with cardiac and vascular events (CVEs) were evaluated. Two established pharmacovigilance methods, reporting odds ratio (ROR) and information components (IC) based statistical shrinkage, were used to measure disproportionality. Results: In total 62,140 CVE records associated with PPI use were investigated. Women showed a higher proportion (54.37%) of PPI-associated CVEs. The median time from PPI initiation to CVE onset was 97 [interquartile range (IQR): 8-491] days, with the shortest median time of 42 days (IQR: 2-277 days) for esomeprazole, and the longest time of 389 days (IQR: 0-525 days) for dexlansoprazole. Although PPIs were not associated with elevated CVE risks compared those of the whole database (IC025/ROR025 = -0.39/0.74), various signals emerged. Despite some similarities exist between the PPIs, their cardiac and vascular safety profiles varied significantly. Pantoprazole showed the broadest spectrum of signals, from thrombotic thrombocytopenic purpura (IC025/ROR025 = 0.01/1.08) to renal haemangioma (IC025/ROR025 = 3.14/9.58). Esomeprazole showed the second-broadest spectrum of toxicities, ranging from duodenal ulcer hemorrhage (IC025/ROR025 = 0.07/1.28) to hypertensive nephropathy (IC025/ROR025 = 4.09/18.72). Vascular signals were more dominant than cardiac signals, suggesting that vascular function was more heavily affected. Hypertensive nephropathy, renal haemangioma, renal artery stenosis, and renal infarct had strong signals across most PPI regimens and merited further attention. Conclusions: PPIs may inflict various CVEs, particularly those involving the vascular system, on the users. Given the wide range of onset times and different toxicity profiles for various PPI medications, they should be prescribed with caution.

Drug-induced Stevens-Johnson syndrome: a disproportionality analysis from the pharmacovigilance database of the World Health Organization.

BACKGROUND: Stevens-Johnson syndrome is a rare but serious skin condition, which can lead to death. Stevens-Johnson syndrome is usually attributed to drug-induced reactions, thus making it vital for clinicians to prevent its occurrence by knowing the trigger drugs. The objective of this study was to comprehensively and systematically excavate the drugs that cause SJS to provide references for clinician. RESEARCH DESIGN AND METHODS: This is an observational, retrospective study, conducting a disproportionality analysis. Where the Information Component (IC) method and Reporting odds ratio (ROR) are used to mine the drugs that cause SJS. RESULTS: A total of 17,787,905 reports were extracted from VigiBase database, of which 25,051 reports were related to SJS. The 18-44 age group had the largest number of cases (N=7,973, 31.83%). A total of 295 drugs was detected as signals. Allopurinol (IC025/ROR025=5.86/69.84), phenytoin (IC025/ROR025=5.60/57.65) and carbamazepine (IC025/ROR025=5.25/43.88) were the top 3 strongest signals. Our study only considered the possibility of SJS caused by a single drug. CONCLUSIONS: Allopurinol, phenytoin and carbamazepine were three strongest signals. Garenoxaci, carbocisteine and dimetindene were strong signals, but there are no relevant cases reported on PubMed or specific SJS in labels, which need further study to verify.

Adverse events of alpelisib: A postmarketing study of the World Health Organization pharmacovigilance database.

AIMS: To explore and describe the adverse reaction signals in the safety reporting for alpelisib. METHODS: We performed a disproportionality analysis of the World Health Organization's VigiBase pharmacovigilance database from 1 January 2019 to 30 June 2021. Disproportionality analysis by information components (ICs) were used to evaluate the potential association between adverse events (AEs) and alpelisib. RESULTS: A total of 33 327 reports were extracted, 5695 of them were chosen with alpelisib as the suspected drug. After combining the same ID, 687 cases remained. The 45-64-years group had the most cases (n = 203, 29.55%). There were 129 Preferred Terms with significant signals. Hyperglycaemia (IC025 = 6.74), breast cancer metastatic (IC025 = 5.85) and metastases to liver (IC025 = 4.70) were the AEs with the strongest signal. AEs with the most cases were hyperglycaemia (n = 595), rash (n = 535) and diarrhoea (n = 475). CONCLUSION: We established a comprehensive list of AEs potentially associated with alpelisib. AEs with the most significant signals were hyperglycaemia, breast cancer metastatic, metastases to liver. The AEs with the most cases were hyperglycaemia, rash, diarrhoea, blood glucose increase and nausea.

How neighborhood environment modified the effects of power outages on multiple health outcomes in New York state?

Background: Although power outage (PO) is one of the most important consequences of increasing weather extremes and the health impact of POs has been reported previously, studies on the neighborhood environment underlying the population vulnerability in such situations are limited. This study aimed to identify dominant neighborhood environmental predictors which modified the impact of POs on multiple health outcomes in New York State. Methods: We applied a two-stage approach. In the first stage, we used time series analysis to determine the impact of POs (versus non-PO periods) on multiple health outcomes in each power operating division in New York State, 2001-2013. In the second stage, we classified divisions as risk-elevated and non-elevated, then developed predictive models for the elevation status based on 36 neighborhood environmental factors using random forest and gradient boosted trees. Results: Consistent across different outcomes, we found predictors representing greater urbanization, particularly, the proportion of residents having access to public transportation (importance ranging from 4.9-15.6%), population density (3.3-16.1%), per capita income (2.3-10.7%), and the density of public infrastructure (0.8-8.5%), were associated with a higher possibility of risk elevation following power outages. Additionally, the percent of minority (-6.3-27.9%) and those with limited English (2.2-8.1%), the percent of sandy soil (6.5-11.8%), and average soil temperature (3.0-15.7%) were also dominant predictors for multiple outcomes. Spatial hotspots of vulnerability generally were located surrounding New York City and in the northwest, the pattern of which was consistent with socioeconomic status. Conclusion: Population vulnerability during power outages was dominated by neighborhood environmental factors representing greater urbanization.

Cardiovascular Toxicity of Carfilzomib: The Real-World Evidence Based on the Adverse Event Reporting System Database of the FDA, the United States.

Background: Carfilzomib, an effective proteasome inhibitor agent for the therapy of relapsed and refractory multiple myeloma, has been related to a significant number of cardiovascular events. However, patterns of cardiovascular complications associated with this agent remain poorly characterized in real-world settings. Objective: To gain further insight into the frequency, spectrum, clinical features, timing, and outcomes of carfilzomib-related cardiovascular toxicities. Methods: This disproportionality (case/non-case) study was conducted leveraging records from FAERS database from 2014 to 2019. Cardiovascular events were defined and broadly categorized eight entities using narrow version of the Standardized MedDRA Queries (SMQs). Reporting odds ratios (ROR) and information component (IC) were calculated to measure disproportionality. Additionally, statistical shrinkage was applied to reduce false-positive signals. Results: The final number of records involved was 28,479,963, with 3,370 records submitted for carfilzomib related cardiovascular events. Significant disproportionality association between carfilzomib administration and cardiovascular events was captured (IC025/ROR025 = 0.85/1.95) when exploring in the entire database. Upon further analysis, all eight broad categories of cardiovascular toxicities were disproportionately associated with carfilzomib with varying frequencies, time-to-onset, and severities. Cardiomyopathy-related complications (N = 1,301, 38.61%), embolic and thrombotic events (N = 821, 24.36%), and cardiac failure (N = 765, 22.70%) largely comprised the reported problems. Notably, the strongest signal was detected for cardiac failure (IC025/ROR025 = 1.33/2.59), followed by pulmonary hypertension (IC025/ROR025 = 1.19/2.34). Median onset time of cardiovascular events was 41days (Q1-Q3: 9-114 days), with the shortest median time being 16 days (Q1-Q3: 4-85 days) for ischemic heart disease, with the longest time being 68 days (Q1-Q3: 21-139 days) for embolic and thrombotic events. Torsade de pointes/QT prolongation was identified as a new complication (IC025/ROR025 = 0.33/1.29) and was particularly noteworthy for highest death proportion (44.11%). Conclusions: Treatment with carfilzomib can lead to severe and versatile cardiovascular events. Early and intensive monitoring is important, particularly in the first 3 months after carfilzomib initiation. Maximizing the benefit while reducing potential cardiovascular harms of carfilzomib should become a priority.

Atrial fibrillation in critically ill patients who received prolonged mechanical ventilation: a nationwide inpatient report.

BACKGROUND/AIMS: To evaluate temporal trends of atrial fibrillation (AF) prevalence in critically ill patients who received prolonged mechanical ventilation (MV) in the United States. METHODS: We used the 2008 to 2014 National Inpatient Sample to compute the weighted prevalence of AF among hospitalized adult patients on prolonged MV. We used multivariable-adjusted models to evaluate the association of AF with clinical factors, in-hospital mortality, hospitalization cost, and length of stay (LOS). RESULTS: We identified 2,578,165 patients who received prolonged MV (21.27% of AF patients). The prevalence of AF increased from 14.63% in 2008 to 24.43% in 2014 (p for trend < 0.0001). Amongst different phenotypes of critically ill patients, the prevalence of AF increased in patients with severe sepsis, asthma exacerbation, congestive heart failure exacerbation, acute stroke, and cardiac arrest. Older age, male sex, white race, medicare access, higher income, urban teaching hospital setting, and Western region were associated with a higher prevalence of AF. AF in critical illness was a risk factor for in-hospital death (odds ratio, 1.13; 95% confidence interval, 1.11 to 1.15), but in-hospital mortality in critically ill patients with AF decreased from 11.6% to 8.3%. AF was linked to prolonged LOS (2%, p < 0.0001) and high hospitalization cost (4%, p < 0.0001). LOS (-1%, p < 0.0001) and hospitalization cost (-4%, p < 0.0001) decreased yearly. CONCLUSION: The prevalence of comorbid AF is increasing, particularly in older patients. AF may lead to poorer prognosis, and high-quality intensive care is imperative for this population.

Cardiotoxicity Induced by Immune Checkpoint Inhibitors: A Pharmacovigilance Study From 2014 to 2019 Based on FAERS.

This study was to scientifically and systematically explore the association between cardiotoxicity and immune checkpoint inhibitors (ICIs) and also to characterize the spectrum of ICI-related cardiac complications. From the first quarter of 2014 to the fourth quarter of 2019, data from the FDA Adverse Event Reporting System database were selected to conduct the disproportionality analysis. Reporting odds ratios and information components were used to evaluate the signal after statistical shrinkage transformation. In total, 7,443,137 cases and 36,326,611 drug-adverse event pairs were collected, among which 9,271 cases were identified to be related to ICI-induced cardiotoxicities. The number of male patients was much higher than that of females (5,579 vs. 3,031) and males presented a slightly higher reporting frequency than females in general, which was statistically significant (ROR = 1.04, 95%CI: 0.99-1.09, p < 0.001). Simultaneously, the proportion of serious or life-threatening outcomes in males was significantly higher than in females (ROR = 1.05, 95%CI: 0.96-1.15, p < 0.001). Importantly, ICIs were associated with over-reporting frequencies of cardiotoxicities in general (ROR025 = 1.06, IC025 = 0.08). PD-1 and PD-L1 were found to be related to cardiac adverse events, corresponding to ROR025 = 1.06, IC025 = 0.08, and ROR025 = 1.06, IC025 = 0.08, respectively, while anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) was significantly associated with some specific adverse events rather than common adverse events. The spectrum of cardiotoxicities induced by ICIs mostly differed among individual agents, but also demonstrated some common features. Dyspnea (N = 2,527, 21.25%), myocarditis (N = 614, 5.16%), atrial fibrillation (N = 576, 4.84%), cardiac failure (N = 476, 4.00%), and pericardial effusion (N = 423, 3.56%) were the top five cardiac adverse events reported in the database. Among them, myocarditis was the only one caused by all ICIs with strong signal value and high risk, warranting further attention. Overall, this investigation mainly showed the profile of cardiotoxicities caused by ICIs, which varied between different ICI therapies, but also shared some similarities in specific symptoms such as myocarditis. Therefore, it is vital and urgent to recognize and manage ICI-related cardiotoxicities, known to frequently occur in clinical practice, at the earliest point.

Synergistic Effects of Anaerobic Co-Digestion of Pretreated Corn Stover with Chicken Manure and Its Kinetics.

The pretreatment effects and synergistic effects of anaerobic co-digestion of pretreated corn stover (CS) with chicken manure (CM) were studied. Results showed that the NaOH-H2O2 pretreatment effect on CS was better than urea pretreatment in terms of anaerobic digestion promotion. The highest cumulative methane yield of 332.7 mL/g VS added was obtained from the CS (NaOH-H2O2 pretreated)/CM ratio of 1:3, and the highest cumulative methane yield of 319.7 mL/g VS added was obtained from the CS (urea pretreated)/CM ratio of 1:2. Synergistic effects were found in CS (NaOH-H2O2 pretreated)/CM ratios of 2:1, 1:2, 1:3 and CS (urea pretreated)/CM ratios of 1:1, 1:2. Synergistic effect was not found at CS (unpretreated)/CM ratios of 1:2 and 1:3. Pretreatment of CS can produce synergistic effect on anaerobic co-digestion and increase cumulative methane yield by 6.54-24.65%. Among the four kinetic models, modified Gompertz model was best fitted in describing the methane production during anaerobic co-digestion (R2 = 0.9845-0.9988).

Ear and labyrinth toxicities induced by immune checkpoint inhibitors: a disproportionality analysis from 2014 to 2019.

Aim: We aimed to systematically characterize ear and labyrinth toxicities after immune checkpoint inhibitors (ICIs) initiation. Materials & methods: Data were extracted from the US FDA Adverse Event Reporting System database. Disproportionality analysis including information component and reporting odds ratio (ROR) was performed to access potential signals. Results: In FDA Adverse Event Reporting System database, 284 records for ICIs-associated ear/labyrinth adverse events (AEs) were involved. In general, there was no significant association between total ICIs use and total ear and labyrinth AEs (ROR025: 0.576). However, in ICIs monotherapy and polytherapy groups, signals were detected in several specific ear and labyrinth AEs. Conclusion: Total ear and labyrinth toxicities were not significantly reported with ICI immunotherapy, while class-specific ear toxicities were detected in some strategies.

Disruption of profilin1 function suppresses developmental and pathological retinal neovascularization.

Angiogenesis-mediated neovascularization in the eye is usually associated with visual complications. Pathological angiogenesis is particularly prominent in the retina in the settings of proliferative diabetic retinopathy, in which it can lead to permanent loss of vision. In this study, by bioinformatics analyses, we provide evidence for elevated expression of actin-binding protein PFN1 (profilin1) in the retinal vascular endothelial cells (VECs) of individuals with proliferative diabetic retinopathy, findings further supported by gene expression analyses for PFN1 in experimentally induced abnormal retinal neovascularization in an oxygen-induced retinopathy murine model. We observed that in a conditional knockout mouse model, postnatal deletion of the Pfn1 gene in VECs leads to defects in tip cell activity (marked by impaired filopodial protrusions) and reduced vascular sprouting, resulting in hypovascularization during developmental angiogenesis in the retina. Consistent with these findings, an investigative small molecule compound targeting the PFN1-actin interaction reduced random motility, proliferation, and cord morphogenesis of retinal VECs in vitro and experimentally induced abnormal retinal neovascularization in vivo In summary, these findings provide the first direct in vivo evidence that PFN1 is required for formation of actin-based protrusive structures and developmental angiogenesis in the retina. The proof of concept of susceptibility of abnormal angiogenesis to small molecule intervention of PFN1-actin interaction reported here lays a conceptual foundation for targeting PFN1 as a possible strategy in angiogenesis-dependent retinal diseases.

Ferulic acid ameliorates nonalcoholic fatty liver disease and modulates the gut microbiota composition in high-fat diet fed ApoE-/- mice.

The objective of this study was to investigate the effects of ferulic acid (FA) on nonalcoholic fatty liver disease (NAFLD) and gut microbiota, and its regulation mechanism in ApoE-/- mice fed on a high-fat diet (HFD). Liver morphology, blood lipids, gut microbiota and their metabolite indole-3-acetic acid (I3A) were determined in ApoE-/- mice. We also examined the hepatic expression of aryl hydrocarbon receptor (AHR), which inhibits the expression of fatty acid synthase (FASN) and sterol regulatory element-binding protein 1c (SREBP-1c), and ultimately reduces the deposition of triglycerides (TG) and total cholesterol (TC) in the liver. The results of the animal experiment showed that oral administration of FA markedly alleviated the formation of NAFLD and decreased the levels of serum TC, TG and low-density lipoprotein cholesterol (LDL-C). Furthermore, FA supplementation altered the composition of gut microbiota, in particular, modulating the ratio of Firmicutes to Bacteroidetes, and decreased the generation of I3A. Additionally, FA could increase the expression of hepatic AHR and inhibit the expression of FASN and SREBP-1c in the liver. Finally, we found that FA did not have hepatorenal toxicity. The findings above illustrate that FA has the potential to ameliorate NAFLD, some of which are closely related to the modulation of specific gut microbiota and the regulation of genes involved in TG and TC metabolism.

Unusual case of primary spontaneous hemopneumothorax in a young man with atypical tension pneumothorax: a case report.

BACKGROUND: Spontaneous life-threatening hemopneumothorax is an atypical but treatable entity of unexpected circulatory collapse in young patients, affecting 0.5-11.6% of patients with primary spontaneous pneumothorax. Spontaneous pneumothorax is a well-documented disorder with a classic clinical presentation of acute onset chest pain and shortness of breath. This disorder might be complicated by the development of hemopneumothorax or tension pneumothorax. CASE PRESENTATION: A 23-year-old Asian man was referred to the emergency room of Xiamen Chang Gung Memorial Hospital with a 1-day history of right-sided chest pain that had been aggravated for 1 hour. A physical examination revealed a young man who was awake and alert but in mild to moderate painful distress. His vital parameters were relatively stable at first. The examining physician noted slight tenderness along the right posterolateral chest wall along the eighth and tenth ribs. Primary spontaneous pneumothorax was considered, and a standing chest X-ray confirmed the diagnosis. A right thoracostomy tube was immediately placed under sterile conditions, and he was referred to the respiratory service. While in the respiratory department, approximately 420 mL of blood was drained from the thoracostomy tube over 15 minutes. Our patient developed obvious hemodynamic instability with hypovolemic shock and was subsequently admitted to the cardiothoracic surgical ward after fluid resuscitation. During the ensuing 4 hours after admission, 750 mL of blood was drained through the thoracostomy tube. A bedside chest X-ray was requested after he was temporarily hemodynamically stabilized. Primary spontaneous hemopneumothorax associated with right tension pneumothorax was considered based on the radiological impression and clinical signs. An emergency limited posterolateral thoracotomy was performed. A standing chest X-ray performed on day 6 of admission after the removal of the thoracostomy tube showed a complete re-expansion of his right lung. He remained stable and was discharged within 1 week. CONCLUSIONS: The successful treatment of a large spontaneous hemopneumothorax depends on early recognition, proactive intervention, and early consideration by a cardiothoracic surgeon. Once the diagnosis is confirmed, early thoracotomy should be considered. Such an aggressive surgery not only leads to shorter hospitalization but also confers better long-term outcomes.

Yifuning postpones ovarian aging through antioxidant mechanisms and suppression of the Rb/p53 signal transduction pathway.

Yifuning is a traditional Chinese medicine recipe that has been used for many years in China for its effects on treating climacteric syndrome in women. The present study aimed to demonstrate the effects and underlying molecular mechanism of Yifuning on the ovaries of aging rats. Selected aging rats were administered different doses of Yifuning (1.0 or 2.0 g/kg by lavage), and after 6 weeks the rats were sacrificed. The activit of indicators of oxidative stress in the serum were measured. The expression levels of 8-oxo-2'-deoxyguanosine (8-OHDG) and p53 in the ovaries were examined using immunohistochemistry. The expression levels of the corresponding genes and proteins were detected by reverse transcription­quantitative polymerase chain reaction and western blotting analyses, respectively. The results indicated that Yifuning significantly prevented ovarian failure, as indicated by improvements in estrous cycling, reproductive organ weights and sex hormone serum levels. Yifuning significantly increased the levels of superoxide dismutase, glutathione peroxidase, catalase and reduced malondialdehyde and hydrogen peroxide levels. Yifuning reduced DNA damage in the ovaries by reducing the expression of 8­OHDG and p53. Treatment with Yifuning significantly reduced the age­induced p19, p53, p21 and Rb activity in the ovaries. The present study demonstrates that Yifuning prevents ovarian failure and the mechanism involved is partly associated with antioxidants and suppression of the Rb/p53 signal transduction pathway.

Bis-cyclopropane analog of disorazole C1 is a microtubule-destabilizing agent active in ABCB1-overexpressing human colon cancer cells.

The novel, chemically stabilized disorazole analog, (-)-CP2-disorazole C1 (1) displayed potent anti-proliferative activity against a broad-spectrum of human colorectal cancer cells. HCT15 and H630R1 cell lines expressing high basal levels of the ABCB1 protein, known to cause multi-drug resistance, were also sensitive to growth inhibition by 1 but were resistant to both vincristine and docetaxel, two commonly used microtubule inhibitors. Compound 1 exhibited strong inhibition of tubulin polymerization at a level comparable to vincristine. In addition, treatment with 1 resulted in decreased protein levels of ß-tubulin but not α-tubulin. An analysis of cellular proteins known to interact with microtubules showed that 1 caused decreased expression of c-Myc, APC, Rb, and additional key cellular signaling pathways in CRC cells. Treatment with compound 1 also resulted in G2/M cell cycle arrest and induction of apoptosis, but not senescence. Furthermore, endothelial spheroid sprouting assays demonstrated that 1 suppressed angiogenesis and can, therefore, potentially prevent cancer cells from spreading and metastasizing. Taken together, these findings suggest that the microtubule disruptor 1 may be a potential drug candidate for the treatment of mCRC.