Association of preoperative coronavirus disease 2019 with mortality, respiratory morbidity and extrapulmonary complications after elective, noncardiac surgery: An observational cohort study.

STUDY OBJECTIVE: To assess the impact of preoperative infection with the contemporary strain of severe acute respiratory coronavirus 2 (SARS-CoV-2) on postoperative mortality, respiratory morbidity and extrapulmonary complications after elective, noncardiac surgery. DESIGN: An ambidirectional observational cohort study. SETTING: A tertiary and teaching hospital in Shanghai, China. PATIENTS: All adult patients (≥ 18 years of age) who underwent elective, noncardiac surgery under general anesthesia at Huashan Hospital of Fudan University from January until March 2023 were screened for eligibility. A total of 2907 patients were included. EXPOSURE: Preoperative coronavirus disease 2019 (COVID-19) positivity. MEASUREMENTS: The primary outcome was 30-day postoperative mortality. The secondary outcomes included postoperative pulmonary complications (PPCs), myocardial injury after noncardiac surgery (MINS), acute kidney injury (AKI), postoperative delirium (POD) and postoperative sleep quality. Multivariable logistic regression was used to assess the risk of postoperative mortality and morbidity imposed by preoperative COVID-19. MAIN RESULTS: The risk of 30-day postoperative mortality was not associated with preoperative COVID-19 [adjusted odds ratio (aOR), 95% confidence interval (CI): 0.40, 0.13-1.28, P = 0.123] or operation timing relative to diagnosis. Preoperative COVID-19 did not increase the risk of PPCs (aOR, 95% CI: 0.99, 0.71-1.38, P = 0.944), MINS (aOR, 95% CI: 0.54, 0.22-1.30; P = 0.168), or AKI (aOR, 95% CI: 0.34, 0.10-1.09; P = 0.070) or affect postoperative sleep quality. Patients who underwent surgery within 7 weeks after COVID-19 had increased odds of developing delirium (aOR, 95% CI: 2.26, 1.05-4.86, P = 0.036). CONCLUSIONS: Preoperative COVID-19 or timing of surgery relative to diagnosis did not confer any added risk of 30-day postoperative mortality, PPCs, MINS or AKI. However, recent COVID-19 increased the risk of POD. Perioperative brain health should be considered during preoperative risk assessment for COVID-19 survivors.

A new abietane diterpenoid from Lycopodium complanatum.

A new abietane diterpenoid, 1ß, 11-epoxyabieta-12-hydroxy-8, 11, 13-triene-7-one (1), along with three known compounds (2-4), was isolated from Lycopodium complanatum. Their structures were confirmed by the analysis of 1D, 2D NMR and HRESIMS data, and comparison with previous spectral data. All compounds were tested for inhibitory activities against A549, HepG2 and MCF-7 tumor cell lines. [Figure: see text].

LncRNA-mediated effects of vitrification temperatures and cryoprotectant concentrations on bovine oocyte development following vitrification at the GV stage.

We evaluated the effects of different vitrification temperatures (VTs) and cryoprotective agent concentrations (CPAs) on the viability and expressions of long non-coding RNA (lncRNA) in bovine oocytes following vitrification at the germinal vesicle (GV) stage. Our findings provide a theoretical support for improvement of the cryopreservation technology of bovine immature oocytes (BIOs). Bovine cumulus oocyte complexes (COCs) were collected and randomized into five groups: fresh oocytes (control), oocytes vitrified in liquid helium (LHe; -269 °C) with 5.6 M CPAs (LHe 5.6 M), oocytes vitrified in LHe with 6.6 M CPAs (LHe 6.6 M), oocytes vitrified in liquid nitrogen (LN; -196 °C) with 5.6 M CPAs (LN 5.6 M), and oocytes vitrified in LN with 6.6 M CPAs (LN 6.6 M). Of the four vitrification groups, the LHe 5.6 M group exhibited the highest blastocyst rate (13.22%), followed by the LHe 6.6 M group (10.19%) and LN 6.6 M group (9.77%), while the LN 5.6 M group had the lowest blastocyst rate (1.87%). Then, lncRNA expressions in the five groups were profiled. A total of 18,271 lncRNAs were identified, of which 2,158 were differentially expressed lncRNAs (DELs) in the vitrified groups, compared to the fresh group (P < 0.05; fold-change > 2). Co-location (cis) and co-expression (trans) prediction revealed 14 differentially expressed target genes (DETGs), which corresponded to 17 DELs. Based on grouping data and expression profiles of the DELs, we demonstrated that different VTs (-269 °C vs. -196 °C) can affect the expressions of MSTRG.12295.5, MSTRG.37123.1, MSTRG.37930.2, MSTRG.40464.9, MSTRG.8869.3 and MSTRG.26680.6. Expressions of these lncRNAs were affected by CPAs only in the condition of vitrification with LHe (-269 °C). Expressions of MSTRG.35129.6 were associated with exposures to both VTs and CPAs; while expressions of MSTRG.3578.3, MSTRG.40576.3, MSTRG.6723.5, MSTRG.32862.4, MSTRG.1184.4, MSTRG.33110.3, MSTRG.40454.2, MSTRG.41073.2, MSTRG.44732.4 and MSTRG.6729.3 might be related to vitrification. Co-expression analysis showed that MSTRG.12295.5, MSTRG.37930.2, MSTRG.40454.2, MSTRG.8869.3 and MSTRG.6723.5 expressions affect oocyte development after vitrification by regulating target gene expressions. Taken together, improvement of the developmental ability of BIOs after LHe vitrification maybe attributed to changes in expressions of some lncRNAs. Our findings elucidate on the molecular mechanisms underlying the development of BIOs under different VTs and CPAs.

Comparison of 1.0 g/kg of 20% mannitol initiated at different time points and effects on brain relaxation in patients with midline shift undergoing supratentorial tumor resection: a randomized controlled trial.

OBJECTIVE: Previous studies have suggested the use of 1.0 g/kg of 20% mannitol at the time of skin incision during neurosurgery in order to improve brain relaxation. However, the incidence of brain swelling upon dural opening is still high with this dose. In the present study, the authors sought to determine a better timing for mannitol infusion. METHODS: One hundred patients with midline shift who were undergoing elective supratentorial tumor resection were randomly assigned to receive early (immediately after anesthesia induction) or routine (at the time of skin incision) administration of 1.0 g/kg body weight of 20% mannitol. The primary outcome was the 4-point brain relaxation score (BRS) immediately after dural opening (1, perfectly relaxed; 2, satisfactorily relaxed; 3, firm brain; and 4, bulging brain). The secondary outcomes included subdural intracranial pressure (ICP) measured immediately before dural opening; serum osmolality and osmole gap (OG) measured immediately before mannitol infusion (T0) and at the time of dural opening (TD); changes in serum electrolytes, lactate, and hemodynamic parameters at T0 and 30, 60, 90, and 120 minutes thereafter; and fluid balance at TD. RESULTS: The time from the start of mannitol administration to dural opening was significantly longer in the early administration group than in the routine administration group (median 66 [IQR 55-75] vs 40 [IQR 38-45] minutes, p < 0.001). The BRS (score 1/2/3/4, n = 14/26/9/1 vs 3/25/18/4, p = 0.001) was better and the subdural ICP (median 5 [IQR 3-6] vs 7 [IQR 5-10] mm Hg, p < 0.001) was significantly lower in the early administration group than in the routine administration group. Serum osmolality and OG increased significantly at TD compared to levels at T0 in both groups (all p < 0.001). Intergroup comparison showed that serum osmolality and OG at TD were significantly higher in the routine administration group (p < 0.001 and = 0.002, respectively). Patients who had received early administration of mannitol had more urine output (p = 0.001) and less positive fluid balance (p < 0.001) at TD. Hemodynamic parameters, serum lactate concentrations, and incidences of electrolyte disturbances were comparable between the two groups. CONCLUSIONS: Prolonging the time interval between the start of mannitol infusion and dural incision from approximately 40 to 66 minutes can improve brain relaxation and decrease subdural ICP in elective supratentorial tumor resection.

L-Type Amino Acid Transporter 1 Regulates Cancer Stemness and the Expression of Programmed Cell Death 1 Ligand 1 in Lung Cancer Cells.

The l-type amino acid transporter 1 (LAT1) is a membranous transporter that transports neutral amino acids for cells and is dysregulated in various types of cancer. Here, we first observed increased LAT1 expression in pemetrexed-resistant non-small cell lung cancer (NSCLC) cells with high cancer stem cell (CSC) activity, and its mRNA expression level was associated with shorter overall survival in the lung adenocarcinoma dataset of the Cancer Genome Atlas database. The inhibition of LAT1 by a small molecule inhibitor, JPH203, or by RNA interference led to a significant reduction in tumorsphere formation and the downregulation of several cancer stemness genes in NSCLC cells through decreased AKT serine/threonine kinase (AKT)/mammalian target of rapamycin (mTOR) activation. The treatment of the cell-permeable leucine derivative promoted AKT/mTOR phosphorylation and reversed the inhibitory effect of JPH203 in the reduction of CSC activity in pemetrexed-resistant lung cancer cells. Furthermore, we observed that LAT1 silencing caused the downregulation of programmed cell death 1 ligand 1 (PD-L1) on lung cancer cells. The PD-L1+/LAT1+ subpopulation of NSCLC cells displayed great CSC activity with increased expression of several cancer stemness genes. These data suggest that LAT1 inhibitors can serve as anti-CSC agents and could be used in combination with immune checkpoint inhibitors in lung cancer therapy.

Effect of strict intraoperative blood pressure management strategy on postoperative acute kidney injury in non-cardiac surgery: A meta-analysis of randomised controlled trials.

BACKGROUND: Acute kidney injury (AKI) is one of the most serious perioperative complications. 20% to 40% of high-risk patients who undergo non-cardiac surgery have AKI and those with AKI are eight-times more likely to die within 30 days after surgery. It may be related to intraoperative hypotension, which is mainly caused by vasodilatory and cardiodepressant effects of anaesthesia, and/or hypovolemia. Strict intraoperative blood pressure management strategy (strict BP management) is a potential option to prevent postoperative AKI. This strategy refers to additional administration of vasoactive agents under the premise of a protocolised fluid delivery. The efficacy of strict BP management for preventing postoperative AKI in non-cardiac surgery patients was assessed by a meta-analysis. METHODS: We systematically retrieved randomised controlled trials (RCTs) and compared strict BP management with conventional therapy control on effect of postoperative AKI in non-cardiac surgery patients, which were published on PubMed, EMBASE, Cochrane library and Web of Science databases before October 5, 2020. Ultimately, a meta-analysis of all RCTs eligible for inclusion criteria was performed. RESULTS: Five RCTs, comprising 1485 patients, were included in the meta-analysis. Strict BP management was associated with a reduced incidence of postoperative AKI [relative risk (RR) = 0.73, 95% confidence interval (CI): 0.58-0.92, P = .007]. No significant difference was found between strict BP management group and conventional therapy control in mortality at longest follow-up available (RR = 0.92, 95% CI: 0.68-1.25, P = .60). In the subset analysis, the studies using supranormal BP management target was significantly lower in the incidence of postoperative AKI (RR = 0.65, 95% CI: 0.51-0.82, P = .0003) CONCLUSION: Strict BP management is significantly more effective than conventional therapy for the prevention of postoperative AKI. Supranormal target of intraoperative BP management may be considered a more appealing option for the prevention of AKI.

Relationship between bovine oocytes developmental competence and mRNA expression of apoptotic and mitochondrial genes following the change of vitrification temperatures and cryoprotectant concentrations.

The present study analyzed the relationship between bovine oocytes developmental competence and mRNA expression of apoptotic and mitochondrial genes following the change of vitrification temperatures (VTs) and cryoprotectant agent concentrations (CPAs). Cumulus oocyte complexes were randomly divided into five groups: control, vitrified in liquid nitrogen (LN; -196 °C) with 5.6 M CPAs (LN 5.6 M), LN with 6.6 M CPAs (LN 6.6 M), liquid helium (LHe; -269 °C) with 5.6 M CPAs (LHe 5.6 M), and LHe with 6.6 M CPAs (LHe 6.6 M). After vitrification and warming, oocytes of vitrified and control groups were subjected to in vitro maturation (IVM), in vitro fertilization and in vitro culture. The blastocyst rate in LHe 5.6 M group was the highest among the four vitrified groups (13.7% vs. 9.4%, 1.3%, and 8.4%; P < 0.05). The mRNA expression level of 8 apoptotic- and 12 mitochondria-related genes were detected through qRT-PCR after IVM. Lower VT (LHe, -269 °C) positively affected the mRNA expression levels of apoptotic genes (BAD, BID, BTK, TP53, and TP53I3) and mitochondrial genes (COX6B1, DERA, FIS1, NDUFA1, NDUFA4, PRDX2, SLC25A5, TFB1M, and UQCRB), and reduced oxidative stress from freezing. Decreased CPAs (5.6 M) positively affected mRNA expression levels of apoptotic genes (BAD, BCL2A1, BID, and CASP3) in LHe vitrification but negatively affected apoptotic genes (BAD, BAX, BID, BTK, and BCL2A1) in LN vitrification. In conclusion, decreased VTs and CPAs in LHe vitrification may increase the blastocyst rate by changing the mRNA expression levels of these apoptotic and mitochondrial genes for the vitrified oocytes.

Comparing remifentanil and sufentanil in stress reduction during neurosurgery: a randomised controlled trial.

Background In most scenarios, anaesthesiologists titrate opioids to control nociceptive surgical stress based on intraoperative haemodynamic changes. Remifentanil was reported to cause more profound cardiovascular depression than sufentanil. A concern is that this direct cardiovascular depression might counteract the hypertension and tachycardia caused by surgical manipulation and mask inadequate analgesia. Objective To compare remifentanil and sufentanil, titrated to maintain a comparable haemodynamic range (within 20% of baseline) and combined with the same propofol regimen, in stress reduction measured as plasma levels of putative mediators of surgical stress. Setting Huashan Hospital of Fudan University, Shanghai, China. Method Forty-five patients undergoing supratentorial glioma resection were randomised to the remifentanil group or the sufentanil group. Main outcome measures Plasma concentrations of cortisol, epinephrine, norepinephrine, interleukin-6, interleukin-10 and lymphocyte counts were analysed before anaesthesia, 1 h after incision, at the end of surgery and 24 h after incision using enzyme-linked immunosorbent assay and an automatic haematology analyser. Recovery profiles during emergence from anaesthesia were also compared. Results Except for a lower epinephrine concentration in the remifentanil group 24 h after incision (median [interquartile range], 4.2 [3.4-6.1] vs. 8.4 [4.8-12.5] ng/ml; P = 0.003), stress biomarkers were not significantly different between the two groups. Patients in the sufentanil group had lower grades in coughing, restlessness (P = 0.001 and < 0.001, respectively) and a lower incidence of postoperative shivering (P = 0.007). Conclusion Compared to that of sufentanil, the direct cardiovascular depression of remifentanil does not mask the clinical manifestation of inadequate analgesia when both drugs are titrated according to haemodynamic variables in neurosurgery.

Comparing two airway management strategies for moderately sedated patients undergoing awake craniotomy: A single-blinded randomized controlled trial.

BACKGROUND: In the monitored anesthesia care (MAC) setting for awake craniotomy (AC), maintaining airway patency in sedated patients remains challenging. This randomized controlled trial aimed to compare the validity of the below-epiglottis transnasal tube insertion (the tip of the tube placed between the epiglottis and vocal cords) and the nasopharyngeal airway (simulated by the above-epiglottis transnasal tube with the tip of the tube placed between the epiglottis and the free edge of the soft palate) with respect to maintaining upper airway patency for moderately sedated patients undergoing AC. METHODS: Sixty patients scheduled for elective AC were randomized to receive below-epiglottis (n = 30) or above-epiglottis (n = 30) transnasal tube insertion before surgery. Moderate sedation was maintained in the pre- and post-awake phases. The primary outcome was the upper airway obstruction (UAO) remission rate (relieved obstructions after tube insertion/the total number of obstructions before tube insertion). RESULTS: The UAO remission rate was higher in the below-epiglottis group [100% (12/12) vs 45% (5/11); P = .005]. The tidal volume values monitored through the tube were greater in the below-epiglottis group during the pre-awake phase (P < .001). End-tidal carbon dioxide (EtCO2 ) monitored through the tube was higher in the below-epiglottis group at bone flap removal (P < .001). During the awake phase, patients' ability to speak was not impeded. No patient had serious complications related to the tube. CONCLUSION: The below-epiglottis tube insertion is a more effective method to maintain upper airway patency than the nasopharyngeal airway for moderately sedated patients undergoing AC.

Defining the Vulnerability Window of Anesthesia-Induced Neuroapoptosis in Developing Dentate Gyrus Granule Cells - A Transgenic Approach Utilizing POMC-EGFP Mice.

Exposure to commonly used anesthetics is associated with widespread neuroapoptosis in neonatal animals. Vulnerability of developing hippocampal dentate gyrus granule cells to anesthetic neurotoxicity peaks approximately 2 weeks after cell birth, as measured by bromodeoxyuridine birth dating, regardless of the age of the animal. The present study examined whether the vulnerable window can be further characterized by utilizing a transgenic approach. Proopiomelanocortin enhanced green fluorescent protein (POMC-EGFP) mice (postnatal day 21) were exposed to 3% sevoflurane for 6 h. Following exposure, cleaved caspase 3, expression of EGFP and differential maturational markers were quantified and compared with unanesthetized littermates. Electrophysiological properties of EGFP+ and EGFP- cells in the subgranular zone and the inner half of the granule cell layer were recorded by whole-cell patch-clamp. We found that sevoflurane significantly increased apoptosis of POMC-EGFP+ granule cells that accounted for approximate 1/3 of all apoptotic cells in dentate gyrus. Apoptotic EGFP- granule cells more frequently expressed the immature neuronal marker calretinin (75.4% vs 45.0%, P < 0.001) and less frequently the late progenitor marker NeuroD1 (21.9% vs 87.9%, P < 0.001) than EGFP+ granule cells. Although EGFP- granule cells were more mature in immunostaining than EGFP+ granule cells, their electrophysiological properties partially overlapped in terms of input resistance, resting membrane potential and action potential amplitude. Our results revealed the POMC stage, when GABA acts as an excitatory neurotransmitter, only partly captures susceptibility to anesthetic neurotoxicity, suggesting the vulnerable window of anesthesia-induced neuroapoptosis extends from the end of POMC+ stage to the post-POMC+ stage when depolarizing glutamatergic inputs emerge.

[Effect of intrahippocampal injection of anti-cellular prion protein monoclonal antibody on cognitive deficits in APPswe/PSEN1dE9 transgenic mice].

OBJECTIVE: To study the effects of intrahippocampal injection of cellular prion protein (PrPC) antibody on cognitive deficits of APPswe/PSEN1dE9 transgenic mice. METHODS: Eight-month-old male APPswe/PSEN1dE9 transgenic mice were subjected to bilateral intrahippocampal injection of a single dose (2 µL) of anti-PrPC monoclonal antibody (EP1802Y) or PBS, with wild-type C57Bl/6J mice serving as the control group. After two months, the mice were tested for cognitive behaviors using open filed (OF) test, Morris water maze (MWM) test, fear conditioning (FC) test, and novel object recognition (NOR) test, and immunohistochemistry was used to examine the changes in hippocampal expression of Aß1-42. RESULTS: The EP1802Y-treated and PBS-treated mice showed no significantly differences in the performance in OF test in terms of central activity time or total distance of activity (P>0.05), nor in NOR test in terms of novel object recognition index (P>0.05). In MWM test, the EP1802Y-treated and PBS-treated mice showed significantly reduced crossings of the hidden platform as compared with the wild-type mice (P<0.05), but EP1802Y-treated mice had a significantly shorter swimming distance to find the platform than PBS-treated mice (P<0.05). No significant differences were found in the results of FC test among the 3 groups. Immunohistochemistry revealed a significantly reduced expression of Aß1-42 in the hippocampus of EP1802Y-treated mice. CONCLUSION: Intrahippocampal injection of PrPC antibody can improve cognitive deficits of APPswe/PSEN1dE9 transgenic mice, which sheds light on a novel therapeutic approach for Alzheimer's disease that targets PrPC to lower the toxicity of Aß oligomer.

Cinnamomum verum ingredient 2-methoxycinnamaldehyde: a new antiproliferative drug targeting topoisomerase I and II in human lung squamous cell carcinoma NCI-H520 cells.

Cinnamomum verum has been used as a Chinese herbal medication. We investigated the antiproliferative effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the cortex of the plant, and the molecular biomarkers associated with tumorigenesis in human lung squamous cell carcinoma NCI-H520 cells. The effects of 2-MCA on cell growth, cytotoxicity, apoptosis, and topoisomerase I and II activities in human lung squamous cell carcinoma NCI-H520 cells were evaluated in vitro and in vivo. The results showed that 2-MCA inhibited proliferation and induced apoptosis as implicated by mitochondrial membrane potential (ΔΨm) loss, activation of both caspase 3 and caspase 9, as well as morphological characteristics of apoptosis. Furthermore, 2-MCA also induced lysosomal vacuolation with elevated volume of acidic compartment and cytotoxicity, and inhibited topoisomerase I as well as II activities. Additional study showed the antiproliferative effect of 2-MCA in a nude mice model. In short, our data imply that the antiproliferative activity of 2-MCA in vitro involved downregulation of cell growth markers, both topoisomerase I and II, and upregulation of proapoptotic molecules, associated with increased lysosomal vacuolation. In vivo, 2-MCA reduced the tumor size, which could have had a significant clinical impact. Our data imply that 2-MCA may be a potential agent for chemoprevention as well as anticancer therapy.

Cinnamomum verum component 2-methoxycinnamaldehyde: a novel antiproliferative drug inducing cell death through targeting both topoisomerase I and II in human colorectal adenocarcinoma COLO 205 cells.

BACKGROUND: Cinnamomum verum is used to manufacture the spice cinnamon. In addition, the plant has been used as a Chinese herbal medication. METHODS: We investigated the antiproliferative effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the cortex of the plant, and the molecular biomarkers associated with tumorigenesis in human colorectal adenocarcinoma COLO 205 cells. Specifically, cell viability was evaluated by colorimetric assay; apoptosis was determined by flow cytometry and morphological analysis with bright field, acridine orange, and neutral red stainings, as well as comet assay; topoisomerase I activity was determined by assay based upon DNA relaxation and topoisomerase II by DNA relaxation plus decatentation of kinetoplast DNA; lysosomal vacuolation and volume of acidic compartments (VACs) were determined by neutral red staining. RESULTS: The results demonstrate that 2-MCA inhibited proliferation and induced apoptosis as implicated by mitochondrial membrane potential (ΔΨm) loss, activation of both caspase-3 and -9, increase of annexin V(+)PI(+) cells, as well as morphological characteristics of apoptosis. Furthermore, 2-MCA also induced lysosomal vacuolation with elevated VAC, cytotoxicity, and inhibitions of topoisomerase I as well as II activities. Additional study demonstrated the antiproliferative effect of 2-MCA found in a nude mice model. CONCLUSIONS: Our data implicate that the antiproliferative activity of 2-MCA in vitro involved downregulation of cell growth markers, both topoisomerase I and II, and upregulation of pro-apoptotic molecules, associated with increased lysosomal vacuolation. In vivo 2-MCA reduced the tumor burden that could have significant clinical impact. Indeed, similar effects were found in other tested cell lines, including human hepatocellular carcinoma SK-Hep-1 and Hep 3B, lung adenocarcinoma A549 and squamous cell carcinoma NCI-H520, and T-lymphoblastic MOLT-3 (results not shown). Our data implicate that 2-MCA could be a potential agent for anticancer therapy.

Cuminaldehyde from Cinnamomum verum Induces Cell Death through Targeting Topoisomerase 1 and 2 in Human Colorectal Adenocarcinoma COLO 205 Cells.

Cinnamomum verum, also called true cinnamon tree, is employed to make the seasoning cinnamon. Furthermore, the plant has been used as a traditional Chinese herbal medication. We explored the anticancer effect of cuminaldehyde, an ingredient of the cortex of the plant, as well as the molecular biomarkers associated with carcinogenesis in human colorectal adenocarcinoma COLO 205 cells. The results show that cuminaldehyde suppressed growth and induced apoptosis, as proved by depletion of the mitochondrial membrane potential, activation of both caspase-3 and -9, and morphological features of apoptosis. Moreover, cuminaldehyde also led to lysosomal vacuolation with an upregulated volume of acidic compartment and cytotoxicity, together with inhibitions of both topoisomerase I and II activities. Additional study shows that the anticancer activity of cuminaldehyde was observed in the model of nude mice. Our results suggest that the anticancer activity of cuminaldehyde in vitro involved the suppression of cell proliferative markers, topoisomerase I as well as II, together with increase of pro-apoptotic molecules, associated with upregulated lysosomal vacuolation. On the other hand, in vivo, cuminaldehyde diminished the tumor burden that would have a significant clinical impact. Furthermore, similar effects were observed in other tested cell lines. In short, our data suggest that cuminaldehyde could be a drug for chemopreventive or anticancer therapy.

Discovery of a Novel Anti-Cancer Agent Targeting Both Topoisomerase I & II as Well as Telomerase Activities in Human Lung Adenocarcinoma A549 Cells In Vitro and In Vivo: Cinnamomum verum Component Cuminaldehyde.

Cinnamomum verum is used to make the spice cinnamon and has been used for more than 5000 years by both of the two most ancient forms of medicine in the words: Ayurveda and traditional Chinese herbal medicines for various applications such as adenopathy, rheumatism, dermatosis, dyspepsia, stroke, tumors, elephantiasis, trichomonas, yeast, and virus infections. We evaluated the anticancer effect of cuminaldehyde (CuA), a constituent of the bark of the plant, and its underlying molecular biomarkers associated with carcinogenesis in human lung adenocarcinoma A549 cells. The results show that cuminaldehyde suppressed proliferation and induced apoptosis as indicated by mitochondrial membrane potential loss, activation of caspase 3 and 9, increase in annexin V+PI+ cells, and morphological characteristics of apoptosis, including blebbing of plasma membrane, nuclear condensation, fragmentation, apoptotic body formation, and comet with elevated tail intensity and moment. In addition, cuminaldehyde also induced lysosomal vacuolation with increased volume of acidic compartments (VAC), suppressions of both topoisomerase I & II as well as telomerase activities in a dose-dependent manner. Further study reveals the growth-inhibitory effect of cuminaldehyde was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of cuminaldehyde against A549 cells is accompanied by downregulations of proliferative control involving apoptosis, both topoisomerase I & II as well as telomerase activities, together with an upregulation of lysosomal vacuolation and VAC. Similar effects (including all of the above-mentioned effects) were found in other cell lines, including human lung squamous cell carcinoma NCI-H520 and colorectal adenocarcinoma COLO 205 (results not shown). Our data suggest that cuminaldehyde could be a potential agent for anticancer therapy.

Molecular Mechanism of Cinnamomum verum Component Cuminaldehyde Inhibits Cell Growth and Induces Cell Death in Human Lung Squamous Cell Carcinoma NCI-H520 Cells In Vitro and In Vivo.

Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine. We evaluated the effects and the molecular mechanisms of cuminaldehyde (CuA), a constituent of the bark of Cinnamomum verum, on human lung squamous cell carcinoma NCI-H520 cells. Specifically, cell viability was evaluated by colorimetric assay; cytotoxicity by LDH release; apoptosis was determined by Western blotting, and morphological analysis with, acridine orange and neutral red stainings and comet assay; topoisomerase I activity was assessed using assay based upon DNA relaxation and topoisomerase II by DNA relaxation plus decatentation of kinetoplast DNA; lysosomal vacuolation and volume of acidic compartments (VAC) were evaluated with neutral red staining. The results show that CuA suppressed proliferation and induced apoptosis as indicated by an up-regulation of pro-apoptotic bax and bak genes and a down-regulation of anti-apoptotic bcl-2 and bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase 3 and 9, and morphological characteristics of apoptosis, including blebbing of the plasma membrane, nuclear condensation, fragmentation, apoptotic body formation, and comet with elevated tail intensity and moment. In addition, CuA also induced lysosomal vacuolation with increased VAC, cytotoxicity, as well as suppressions of both topoisomerase I and II activities in a dose-dependent manner. Further study revealed the growth-inhibitory effect of CuA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of CuA against NCI-H520 cells is accompanied by downregulations of proliferative control involving apoptosis and both topoisomerase I and II activities, and upregulation of lysosomal with increased VAC and cytotoxicity. Similar effects were found in other cell lines, including human lung adenocarcinoma A549 cells and colorectal adenocarcinoma COLO 205 (results not shown). Our data suggest that CuA could be a potential agent for anticancer therapy.

Cinnamomum verum Component 2-Methoxycinnamaldehyde: A Novel Anticancer Agent with Both Anti-Topoisomerase I and II Activities in Human Lung Adenocarcinoma A549 Cells In Vitro and In Vivo.

Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine. We evaluated the anticancer effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, and its underlying molecular biomarkers associated with carcinogenesis in human lung adenocarcinoma A549 cells. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by an upregulation of pro-apoptotic Bax and Bak genes and downregulation of anti-apoptotic Bcl-2 and Bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase-3 and -9, and morphological characteristics of apoptosis, including plasma membrane blebbing and long comet tail. In addition, 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartment (VAC) and suppressions of nuclear transcription factors nuclear factor-κB (NF-κB) and both topoisomerase I and II activities. Further study reveals that the growth-inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against A549 cells is accompanied by downregulations of NF-κB binding activity and proliferative control involving apoptosis and both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and VAC. Our data suggest that 2-MCA could be a potential agent for anticancer therapy.

The Ankyrin Repeat Domain 49 (ANKRD49) Augments Autophagy of Serum-Starved GC-1 Cells through the NF-κB Pathway.

The ankyrin repeat domain 49 (ANKRD49) is an evolutionarily conserved protein highly expressed in testes. However, the function of ANKRD49 in spermatogenesis is unknown. In this study, we found that ANKRD49 resides primarily in nucleus of spermatogonia, spermatocytes and round spermatids. ANKRD49 overexpression augments starvation-induced autophagy in male germ GC-1 cells whereas shRNA knockdown of ANKRD49 attenuates the autophagy. Inhibition of NF-κB pathway by its inhibitors or p65 siRNA prevents the ANKRD49-dependent autophagy augmentation, demonstrating that ANKRD49 enhances autophagy via NF-κB pathway. Our findings suggest that ANKRD49 plays an important role in spermatogenesis via promotion of autophagy-dependent survival.

Tuberculosis as a risk factor for systemic lupus erythematosus: results of a nationwide study in Taiwan.

A previous study, with relatively small number of patients, showed that prior Mycobacterium tuberculosis (TB) may precipitate SLE in patients from endemic areas. The purpose of the study was to investigate the relationship between prior TB infection and systemic lupus erythematosus (SLE) from the National Health Insurance Research Database (NHIRD) in Taiwan. Cases of SLE and TB were identified from the NHIRD with corresponding ICD-9 codes 710.0 and 011-018, respectively, from January 2000 to December 2008. A total of 2,721 cases of SLE and 10,823 control subjects were included in data analysis. The average annual incidence rate was 8.1 per 100,000. The annual incidence rates of SLE decreased from 6.38 per 100,000 to 2.55 per 100,000 during 2000-2008. Compared with the control subjects, SLE patients were more likely to be white collar workers (P = 0.0005), reside in highly urbanized areas (P = 0.0140), and have higher incomes (P = 0.0088). TB was much more prevalent in SLE patients than in the control subjects (1.8 vs. 0.9%, P < 0.001). The mean time interval between diagnosis of TB and SLE was 45.58 ± 39.0 months. On multivariate analysis, TB was the greatest potential risk factor for precipitating SLE (OR = 2.11, 95% CI = 1.49-3.00). In addition, patients with co-existing TB and DM had a higher risk of SLE than the control group (OR = 3.91, 95% CI 1.84-8.31). In conclusion, this study suggests that there is an increased risk of precipitating SLE among patients with TB in Taiwan from a nationwide health insurance research dataset. Mycobacterial infections could trigger autoimmune diseases in experimental studies. Furthermore, a study with relatively small number of patients revealed that prior TB may precipitate SLE in patients from endemic areas. There is an increased risk of precipitating SLE among patients with TB in Taiwan from a nationwide health insurance research dataset during a 9-year period.

Secondary spontaneous pneumothorax: which associated conditions benefit from pigtail catheter treatment?

OBJECTIVE: The study aimed to assess the clinical efficacy of pigtail catheter drainage for patients with a first episode of secondary spontaneous pneumothorax (SSP) and different associated conditions. METHODS: We retrospectively reviewed the records of patients with SSP who received pigtail catheter drainage as their initial management between July 2002 and October 2009. A total of 168 patients were included in the analysis; 144 (86%) males and 24 (14%) females with a mean age of 60.3 ± 18.3 years (range, 17-91 years). Data regarding demographic characteristics, pneumothorax size, complications, treatments, length of hospital stay, and associated conditions were analyzed. RESULTS: In total, 118 (70%) patients were successfully treated with pigtail catheter drainage, and 50 (30%) patients required further management. Chronic obstructive lung disease was the most common underlying disease (57% of cases). Secondary spontaneous pneumothorax associated with infectious diseases had a higher rate of treatment failure than SSP associated with obstructive lung conditions (19/38 [50%] successful vs 78/104 [75%] successful, P = .004) and malignancy (19/38 [50%] successful vs 13/16 [81%] successful, P = .021). Moreover, patients with SSP associated with infectious diseases had a longer length of hospital stay than those with obstructive lung conditions (23.8 vs 14.5 days, P = .003) and malignancy (23.8 vs 12.1 days, P = .017). No complications were associated with pigtail catheter drainage. CONCLUSIONS: A higher rate of treatment failure was noted in SSP patients with infectious diseases; thus, pigtail catheter drainage is appropriate as an initial management for patients with SSPs associated with obstructive lung conditions and malignancy.