COMPARATIVE CHEMOMETRIC PROFILES BETWEEN LEAF TISSUES OF WITHANIA SOMNIFERA CULTURED IN VITRO AND FIELD

Objective: Metabolomic profiling of herbal extracts is indispensable to standardize drugs and to inaugurate the scientific basis of their therapeutic properties. The present study was attempted with an objective to investigate a comparative GC-MS (Gas chromatography–Mass spectrometry) analysis of in vitro and field grown leaf tissues of “Indian ginseng”. Methods: GC-MS often serves the methods of option for screening and quantitative metabolite profiling. In the present study, metabolic profiling of methanolic extracts of field and in vitro cultured Withania somnifera (Ashwagandha) leaf tissues were carried out using GC–MS technique. Results: A total number of 39 primary metabolites in leaf were identified. These include alcohols, organic acids, purine, pyrimidine, sugars and putrescine. Highly significant qualitative and quantitative differences were noticed between the leaf tissues cultured in vitro and from the field. Especially, significant elevation in the accumulation of GABA (γ amino butyric acid) and putrescine was recorded in in vitro cultured leaf samples. Conclusion: We conclude that in vitro cultures offers an intrinsic advantage to produce therapeutically valuable compounds, relatively in a short span of time and this principle determine its use as an alternative to field grown sample

β-Lapachone Significantly Increases the Effect of Ionizing Radiation to Cause Mitochondrial Apoptosis via JNK Activation in Cancer Cells

β-lapachone (β-lap), has been known to cause NQO1-dependnet death in cancer cells and sensitize cancer cells to ionizing radiation (IR). We investigated the mechanisms underlying the radiosensitization caused by β-lap. cells induced ROS generation, triggered ER stress and stimulated activation of ERK and JNK. Inhibition of ROS generation by NAC effectively attenuated the activation of ERK and JNK, induction of ER stress, and subsequent apoptosis. Importantly, inhibition of ERK abolished ROS generation and ER stress, whereas inhibition of JNK did not, indicating that positive feedback regulation between ERK activation and ROS generation triggers ER stress in response to combined treatment. Furthermore, prevention of ER stress completely blocked combination treatment-induced JNK activation and subsequent apoptotic cell death. In addition, combined treatment efficiently induced the mitochondrial translocation of cleaved Bax, disrupted mitochondrial membrane potential, and the nuclear translocation of AIF, all of which were efficiently blocked by a JNK inhibitor. Caspases 3, 8 and 9 were activated by combined treatment but inhibition of these caspases did not abolish apoptosis indicating caspase activation played a minor role in the induction of apoptosis. cells are treated with combination of IR and β-lap, positive feedback regulation between ERK and ROS leads to ER stress causing JNK activation and mitochondrial translocation of cleaved Bax. The resultant decrease in mitochondrial membrane leads to translocation of AIF and apoptosis

Unusual Presentation of Cystic Lymphangioma of the Gallbladder

Cystic lymphangioma of the gallbladder is quite a rare tumor with only a few cases having been reported in the literature. We describe here a rare case of cystic lymphangioma of the gallbladder, which was unusual in that the patient presented with biliary pain and an abnormal liver test. Ultrasonography and computed tomography of the abdomen showed a multi-septated cystic mass in the gallbladder fossa and an adjacent compressed gallbladder. Endoscopic retrograde cholangiography showed there was no communication between the bile tract and the lesion, and there were no other abnormal findings with the exception of a laterally compressed gallbladder. After performing endoscopic sphincterotomy, a small amount of sludge was released from the bile duct. The histological findings were consistent with a cystic lymphangioma originating from the subserosal layer of the gallbladder. This unusual clinical presentation of a gallbladder cystic lymphangioma was attributed to biliary sludge, and this was induced by gallbladder dysfunction that was possibly from compression of the gallbladder due to the mass

Prediction for serious bacterial infection in febrile children aged 3 years or younger: comparison of inflammatory markers, the Laboratory-score, and a new laboratory combined model

Purpose To compare the efficacy of inflammatory markers, the Laboratory-score, and a new laboratory combined model for predicting serious bacterial infection (SBI) in young febrile children. Methods The presence of SBI was reviewed in previously healthy children aged 3 years or younger with fever (> 38℃) who visited the emergency department from 2017 through 2018. Areas under the curves (AUCs) of the receiver operating characteristic curve for SBI were compared with individual inflammatory markers (white blood cells [WBC] count, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], procalcitonin [PCT], and urine WBC count), the Laboratory-score, and a laboratory combined model. The latter model was developed using logistic regression analysis including ESR, CRP, and PCT. Results Of the 203 enrolled children, SBI was diagnosed in 58 (28.6%). For SBI prediction, the Laboratory-score showed 51.7% sensitivity (95% confidence interval [CI], 38.2%-65.0%) and 83.5% specificity (95% CI, 76.4%-89.1%). The AUC of the Laboratory-score (0.76) was significantly superior to the values of all individual inflammatory markers (WBC, 0.59 [P = 0.032]; ESR, 0.69; and CRP, 0.74 [P < 0.001]) except that of PCT (0.77, [P < 0.001]). The AUC of the laboratory combined model (0.80) was superior to that of the Laboratory-score (0.76) (P < 0.001). Conclusion In this study, the new laboratory combined model showed good predictability for SBI. This finding suggests the usefulness of combining ESR, CRP, and PCT in predicting SBI

Oral intake of Lactobacillus rhamnosus M21 enhances the survival rate of mice lethally infected with influenza virus

BackgroundInfluenza viruses cause acute respiratory disease. Because of the high genetic variability of viruses, effective vaccines and antiviral agents are limited. Considering the fact that the site of influenza virus entry is the mucosa of the upper respiratory tract, probiotics that can enhance mucosal immunity as well as systemic immunity could be an important source of treatment against influenza infection.MethodsMice were fed with Lactobacillus rhamnosus M21 or skim milk and were challenged with influenza virus. The resulting survival rate, lung inflammation, and changes in the cytokine and secretory immunoglobulin A (sIgA) levels were examined.ResultsBecause of infection (influenza virus), all the mice in the control group and 60% of the mice in the L. rhamnosus M21 group died; however, the remaining 40% of the mice fed with L. rhamnosus M21 survived the infection. Pneumonia was severe in the control group but moderate in the group treated with L. rhamnosus M21. Although there were no significant changes in the proinflammatory cytokines in the lung lysates of mice collected from both groups, levels of interferon-γ and interleukin-2, which are representative cytokines of type I helper T cells, were significantly increased in the L. rhamnosus M21-treated group. An increase in sIgA as well as the diminution of inflammatory cells in bronchoalveolar lavage fluid was also observed in the L. rhamnosus M21-treated group.ConclusionThese results demonstrate that orally administered L. rhamnosus M21 activates humoral as well as cellular immune responses, conferring increased resistance to the host against influenza virus infection

Liver-Specific Deletion of Mouse CTCF Leads to Hepatic Steatosis via Augmented PPARγ Signaling

Background &amp; Aims: The liver is the major organ for metabolizing lipids, and malfunction of the liver leads to various diseases. Nonalcoholic fatty liver disease is rapidly becoming a major health concern worldwide and is characterized by abnormal retention of excess lipids in the liver. CCCTC-binding factor (CTCF) is a highly conserved zinc finger protein that regulates higher-order chromatin organization and is involved in various gene regulation processes. Here, we sought to determine the physiological role of CTCF in hepatic lipid metabolism. Methods: We generated liver-specific, CTCF-ablated and/or CD36 whole-body knockout mice. Overexpression or knockdown of peroxisome proliferator-activated receptor (PPAR)γ in the liver was achieved using adenovirus. Mice were examined for development of hepatic steatosis and inflammation. RNA sequencing was performed to identify genes affected by CTCF depletion. Genome-wide occupancy of H3K27 acetylation, PPARγ, and CTCF were analyzed by chromatin immunoprecipitation sequencing. Genome-wide chromatin interactions were analyzed by in situ Hi-C. Results: Liver-specific, CTCF-deficient mice developed hepatic steatosis and inflammation when fed a standard chow diet. Global analysis of the transcriptome and enhancer landscape revealed that CTCF-depleted liver showed enhanced accumulation of PPARγ in the nucleus, which leads to increased expression of its downstream target genes, including fat storage-related gene CD36, which is involved in the lipid metabolic process. Hepatic steatosis developed in liver-specific, CTCF-deficient mice was ameliorated by repression of PPARγ via pharmacologic blockade or adenovirus-mediated knockdown, but hardly rescued by additional knockout of CD36. Conclusions: Our data indicate that liver-specific deletion of CTCF leads to hepatosteatosis through augmented PPARγ DNA-binding activity, which up-regulates its downstream target genes associated with the lipid metabolic process. © 2021 The Authors1

Analysis of avoidable cardiopulmonary resuscitation incidents with a part-time rapid response system in place

Background: Although a rapid response system (RRS) can reduce the incidence of cardiopulmonary resuscitation (CPR) in general wards, avoidable CPR cases still occur. This study aimed to investigate the incidence and causes of avoidable CPR. Methods: We retrospectively reviewed the medical records of all adult patients who received CPR between April 2013 and March 2016 (35 months) at a tertiary teaching hospital where a part-time RRS was introduced in October 2012. Four experts reviewed all of the CPR cases and determined whether each event was avoidable. Results: A total of 192 CPR cases were identified, and the incidence of CPR was 0.190 per 1,000 patient admissions. Of these, 56 (29.2%) were considered potentially avoidable, with the most common cause being doctor error (n=32, 57.1%), followed by delayed do-not-resuscitate (DNR) placement (n=12, 21.4%) and procedural complications (n=5, 8.9%). The percentage of avoidable CPR was significantly lower in the RRS operating time group than in the RRS non-operating time group (20.7% vs. 35.5%; P=0.026). Among 44 avoidable CPR events (excluding cases related to DNR issues), the rapid response team intervened in only three cases (6.8%), and most of the avoidable CPR cases (65.9%) occurred during the non-operating time. Conclusions: A significant number of avoidable CPR events occurred with a well-functioning, part-time RRS in place. However, RRS operation does appear to lower the occurrence of avoidable CPR. Thus, it is necessary to extend RRS operation time and modify RRS activation criteria. Moreover, policy and cultural changes are needed prior to implementing a full-time RRS