Identifying the stability of housekeeping genes to be used for the quantitative real-time PCR normalization in retinal tissue of streptozotocin-induced diabetic rats

AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl transferase(HPRT),ribosomal protein large P0(36B4)and terminal uridylyl transferase 1(U6)in the diabetic retinal tissue of rat model.METHODS:The expression of these seven genes in rat retinal tissues was determined using real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)in two groups;normal control rats and streptozotocininduced diabetic rats.The stability analysis of gene expression was investigated using geNorm,NormFinder,BestKeeper,and comparative delta-Ct(ΔCt)algorithms.RESULTS:The 36B4 gene was stably expressed in the retinal tissues of normal control animals;however,it was less stable in diabetic retinas.The 18s gene was expressed consistently in both normal control and diabetic rats’retinal tissue.That this gene was the best reference for data normalisation in RT-qPCR studies that used the retinal tissue of streptozotocin-induced diabetic rats.Furthermore,there was no ideal gene stably expressed for use in all experimental settings.CONCLUSION:Identifying relevant genes is a need for achieving RT-qPCR validity and reliability and must be appropriately achieved based on a specific experimental setting.

Vitamin E in the management of pancreatic cancer: A scoping review

Pancreatic cancer is the leading cause of cancer mortality worldwide.Research investigating effective management strategies for pancreatic cancer is ongoing.Vitamin E,consisting of both tocopherol and tocotrienol,has demonstrated debatable effects on pancreatic cancer cells.Therefore,this scoping review aims to summarize the effects of vitamin E on pancreatic cancer.In October 2022,a literature search was conducted using PubMed and Scopus since their inception.Original studies on the effects of vitamin E on pancreatic cancer,including cell cultures,animal models and human clinical trials,were considered for this review.The literature search found 75 articles on this topic,but only 24 articles met the inclusion criteria.The available evidence showed that vitamin E modulated proliferation,cell death,angiogenesis,metastasis and inflammation in pancreatic cancer cells.However,the safety and bioavailability concerns remain to be answered with more extensive preclinical and clinical studies.More in-depth analysis is necessary to investigate further the role of vitamin E in the management of pancreatic cancers.

Effects of time-restricted eating with different eating duration on anthropometrics and cardiometabolic health:A systematic review and meta-analysis

BACKGROUND Time-restricted eating(TRE)is a dietary approach that limits eating to a set number of hours per day.Human studies on the effects of TRE intervention on cardiometabolic health have been contradictory.Heterogeneity in subjects and TRE interventions have led to inconsistency in results.Furthermore,the impact of the duration of eating/fasting in the TRE approach has yet to be fully explored.AIM To analyze the existing literature on the effects of TRE with different eating durations on anthropometrics and cardiometabolic health markers in adults with excessive weight and obesity-related metabolic diseases.METHODS We reviewed a series of prominent scientific databases,including Medline,Scopus,Web of Science,Academic Search Complete,and Cochrane Library articles to identify published clinical trials on daily TRE in adults with excessive weight and obesity-related metabolic diseases.Randomized controlled trials were assessed for methodological rigor and risk of bias using version 2 of the Cochrane risk-of-bias tool for randomized trials(RoB-2).Outcomes of interest include body weight,waist circumference,fat mass,lean body mass,fasting glucose,insulin,HbA1c,homeostasis model assessment for insulin resistance(HOMA-IR),lipid profiles,C-reactive protein,blood pressure,and heart rate.RESULTS Fifteen studies were included in our systematic review.TRE significantly reduces body weight,waist circumference,fat mass,lean body mass,blood glucose,insulin,and triglyceride.However,no significant changes were observed in HbA1c,HOMA-IR,total cholesterol,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,heart rate,systolic and diastolic blood pressure.Furthermore,subgroup analyses based on the duration of the eating window revealed significant variation in the effects of TRE intervention depending on the length of the eating window.CONCLUSION TRE is a promising chrononutrition-based dietary approach for improving anthropometric and cardiometabolic health.However,further clinical trials are needed to determine the optimal eating duration in TRE intervention for cardiovascular disease prevention.

Acute intoxication cases admitted to the emergency department of a university hospital

BACKGROUND: This study aimed to describe the clinical and socio-demographic aspects of acute poisoning in 2010 in Duzce City, Northwest Anatolian Region of Turkey.METHODS: Acute poisoning was due to the intentional ingestion of drugs in young and adult people(≥16), who were treated at the Emergency Service of Duzce University Medical Hospital, Turkey from January 1, 2010 to December 31, 2010. In this retrospective and descriptive study, 95 patients were diagnosed with intoxications and 30 of them intentionally ingested drugs to commit suicide. Records of the patients diagnosed with intoxication were obtained from the Clinical Archive of the hospital. Their diagnoses were established according to the International Statistical Classification of Diseases and Related Health Problems. Codes X60-X84 of this classification were used to classify self-infringed drug injuries and drug poisoning.RESULTS: In this series, 35(36.8%) patients were male and 60 patients(63.2%) female. The male/female ratio was 1.0/1.7. The mean age of the patients was 33.1±14.2 years; 17(17.9%) patients were below 20 years old and 9(9.5%) were older than 50 years. Of these patients, 29(30.5%) were single, 7(7.4%) divorced or separated, and 59(62.1%) married. Their mean time for admission to the emergency service after the incident was 208±180(15–660) minutes. The mean time for admission to the emergency service for patients with food intoxication after the incident was 142±160 minutes, for those with drug intoxication 173±161 minutes, for those with carbon monoxide(CO) intoxication 315±209 minutes, and for those with undefined intoxication 289±166 minutes(P=0.005). Most of the intoxication cases occurred in winter(41.1%, 39 of 95 patients). Admissions to the emergency service were most common in December and April(21 and 16 of 95 patients, respectively). Sixty-five(68.4%) cases were involved in non-deliberate poisoning, whereas 30(31.6%) were involved in deliberate poisoning. Twenty-six of the 95 patients with acute poisonings had mortality risk at admission, however only one died from CO intoxication in the emergency service(1.1%). Suicide attempts were more common in females than in males(21 of 30 patients, 70%, P<0.05). CONCLUSION: In Duzce City of Turkey, most intoxication cases occurred in winter, especially in December. They had non-deliberate poisoning, but deliberate poisoning in suicide attempts was more common in females than in males.

Virological and Molecular Profile of People Living with HIV after 24 Weeks of Treatment with Dolutegravir in Kinshasa

Context: The appointment of the M6 is crucial because it is an indicator of the prognosis of the evolution of the care and the decision-making on the continuation of the AntiRetroViral Treatment. Objective: The objective of this study is therefore to present the virological and molecular profile of People Living with HIV under treatment with Dolutegravir 6 months after being put on ART in Kinshasa. Methods: The present study is a cross-sectional view at the sixth month of a prospective cohort to determine the virological and molecular profile of People Living with HIV (PLHIV) after 6 months of ART based on Dolutegravir (DTG) in Kinshasa. A sample of 5 mL of blood was taken from all HIV patients included. The collection of biological data was carried out under the same conditions as at inclusion. After extraction, Quantitative Real-Time PCR was carried out to determine the quantity of HIV RNA in the samples according to the protocols previously described. Reverse Transcription PCR (RT-PCR) and Nested PCR were carried out to amplify the regions of interest for Protease and Reverse Transcriptase for sequencing. Results: The median VL value was 2.92 log10 RNA copies/mL. With 17.75% of patients experiencing major failure of first-line treatment. Subtype A is dominant with 13 cases (20.98%);followed by CRF_02AG (16.13%), subtypes C (14.52%), D (9.68%) and K (6.45%). The K65R (3 cases), T69P/N (6 cases), K70R (9 cases) and M184V (8 cases) mutations were listed as existing mutations for Nucleotide Reverse Transcriptase Inhibitors. Conclusion: After 6 months of ART, 59.67% of People Living with HIV on Tenofovir-Lamivudine-Dolutegravir is in therapeutic success while 40.33% are in a state of treatment failure. Subtype A remains dominant in the population of PLHIV. Resistance mutations were detected for Lamivudine and Tenofovir, but none for Dolutegravir.

Profile of People Living with HIV after 24 Weeks of Treatment with Dolutegravir in Kinshasa

Introduction: The sixth month appointment (M6) is crucial because at the start of the ART course, it is an indicator of the prognosis of the evolution of care and decision-making on the continuity of treatment. Objective: The objective of this study is therefore to present the profile of People Living with HIV under treatment with Dolutegravir 6 months after starting ART in Kinshasa. Methods: The present study is a cross-sectional view at M6 of a prospective cohort to determine the profile of People Living with HIV (PLHIV) after 6 months of ARV Treatment (ART) in Kinshasa, DRC. During the M6 appointment, from April to August 2022, a sample of 5 ml of blood was taken for the various analyzes from all HIV patients included. The collection of sociodemographic data as well as biological and clinical data was carried out under the same conditions as at inclusion. The parameters recorded during M6 were: age, sex, and religion, level of study, marital status, profession, socio-economic level, height, weight, Body Mass Index (BMI), clinical profile, opportunistic infections as well as biochemical and molecular assessment. Results: In M6, 62 patients were registered including 38 women (61.3%), thus giving a sex ratio of 1.58 in favor of women. Fifty-seven (57) patients did not respond to the appointment, representing a loss rate of 47.89%. The most common age group is between 36 and 45 years old with 16 patients (26.7%). The mean age was 42.4 ± 13.3 years. The mean weight was 60.5 ± 15.4 kg with a mean BMI of 22.6 ± 5.8 kg/m2. Thirty-four (34) patients (61.82%) were in Clinical Stage 3. Thirty-six (36) patients (67.92%) had a normal clinical condition. The most common opportunistic infections among patients in M6 were: skin pruritus (25.8%), dermatitis (22.6%) and rash (21%). The mean values of biochemical parameters of patients in M6 were within normal ranges. The median VL value was 2.92 log10 RNA copies/ml with 17.75% of patients experiencing major failure of first-line treatment. Subtype A is dominant with 13 cases (20.98%);followed by CRF02_AG (16.13%) and C subtypes (14.52%). The mutations K65R (3 cases), T69P/N (6 cases), K70R (9 cases) and M184V (8 cases) were listed in M6. Conclusion: After 6 months of treatment, the majority of patients are in clinical stage 3 with a normal clinical state. Skin infections are the majority opportunistic infections. Certain biological parameters are considerably altered. A high virological failure rate with the presence of certain mutations associated with resistance to Lamivudine and Tenofovir.

Profile of People Living with Human Immunodeficiency Virus Initiating Treatment in the Dolutegravir Era in Kinshasa, Democratic Republic of Congo

Background: For several decades, the introduction of AntiRetrovirals (ARVs) has improved the symptomatology of People Living with HIV (PLHIV), a spectacular reduction in morbidity and mortality, an improvement in life expectancy and quality of life of PLHIV. Objective: The objective of this study was to determine the profile of PLHIV initiating AntiRetroViral Treatment (ART) in the era of Dolutegravir in Kinshasa. Methods: Cross-section of a prospective cohort to determine the profile of PLHIV initiating ART in Kinshasa. The inclusions were from October 04, 2021 to February 15, 2022. Confirmation of the diagnosis was carried out by Nested PCR. The inclusion criteria were: being at least 18 years old, confirmed HIV positive, naïve to ART, consenting and having signed an informed consent. The parameters of interest followed for the present study were: age, sex, religion, level of study, marital status, occupation, height, weight, body mass index (BMI), the clinical profile, the opportunistic infections as well as the para-clinical assessment (biochemistry and molecular biology). Results: 67 (56.3%) women and 52 (43.7%) men were included, thus 119 patients, all confirmed positive for HIV by Nested PCR on the gag, pol and env regions. The average age of the patients included is 39.87 ± 12.36 years and the most represented age group is that of 36 to 45 years with 37 patients (31.9%). The average height was 1.66 ± 0.08 meters, with an average weight of 56.41 ± 13.30 kg, giving an average Body Mass Index (BMI) of 21.54 ± 5.17 kg/m2. The majority of patients were married (46.1%), of Protestant religion (70.7%), with secondary education (66.7%), and working in the informal sector (29.4%). 49 patients (41.5%) were in clinical stage 3 and 55 patients (47.0%) had a normal clinical status. Malaria (45.4%) and tuberculosis (29.4%) were the most common Opportunistic Infections. The mean values of the patients’ assessed biochemical parameters were within the ranges. The median VL value was 4.16 log10 RNA copies/ml. Subtype A (20.2%) is dominant. Mutations K65R (2 cases), T69P/N (5 cases), K70R (9 cases) and M184V (8 cases) were listed. Conclusion: In Kinshasa, PLHIV start ART late. The biochemical parameters evaluated are within normal ranges, with high VLs. Subtype A remains predominant and there are mutations conferring resistance to ART.

Ergogenic Capacity of a 7-Chinese Traditional Medicine Extract in Aged Mice

The ergogenic properties of a 7-Chinese traditional medicine water extract (Ligustrum lucidum ait, LLA), which is composed of the essences of Lycii fructus, Crataegi fructus, Phyllanthi fructus, Chrysanthemi flos, Coicis semen, Ganoderma lucidum, and Zizyphi fructus, were studied using aged mice. Mice were chronically (one month) administered LLA (0.1% and 1%) in the drinking water. Mice pre-treated with LLA showed a good appetite;however, they exhibited a lower rate of body weight increase compared to control mice. In mice subjected to the rotarod test, 1% LLA treatment provided effective adaption to fatigue and significantly increased the duration of mice on the rotarod. In locomotor activity test, 1% LLA potentiated mice mobility and significantly increased rearing behavior. In the antioxidant experiment, 1% LLA treatment significantly increased superoxide dismutase activity in the spleen and liver glutathione levels. These findings suggest that LLA may be utilized as an antifatigue agent, which may function through its antioxidant activity.

Efficacy and safety of over-the-scope clip: Including complications after endoscopic submucosal dissection

AIM: To retrospectively review the results of over-thescope clip (OTSC) use in our hospital and to examine the feasibility of using the OTSC to treat perforations after endoscopic submucosal dissection (ESD). METHODS: We enrolled 23 patients who presented with gastrointestinal (GI) bleeding, fistulae and perforations and were treated with OTSCs (Ovesco Endoscopy GmbH, Tuebingen, Germany) between November 2011 and September 2012. Maximum lesion size was defined as lesion diameter. The number of OTSCs to be used per patient was not decided until the lesion was completely closed. We used a twin grasper (Ovesco Endoscopy GmbH, Tuebingen, Germany) as a grasping device for all the patients. A 9 mm OTSC was chosen for use in the esophagus and colon, and a 10 mm device was used for the stomach, duodenum and rectum. The overall success rate and complications were evaluated, with a particular emphasis on patients who had undergone ESD due to adenocarcinoma. In technical successful cases we included not only complete closing by using OTSCs, but also partial closing where complete closure with OTSCs is almost difficult. In overall clinical successful cases we included only complete closing by using only OTSCs perfectly. All the OTSCs were placed by 2 experienced endoscopists. The sites closed after ESD included not only the perforation site but also all defective ulcers sites.RESULTS: A total of 23 patients [mean age 77 years (range 64-98 years)] underwent OTSC placement during the study period. The indications for OTSC placement were GI bleeding (n = 9), perforation (n = 10), fistula (n = 4) and the prevention of post-ESD duodenal artificial ulcer perforation (n = 1). One patient had a perforation caused by a glycerin enema, after which a fistula formed. Lesion closure using the OTSC alone was successful in 19 out of 23 patients, and overall success rate was 82.6%. A large lesion size (greater than 20 mm) and a delayed diagnosis (more than 1 wk) were the major contributing factors for the overall unsuccessful clinical cases. The location of the unsuccessful lesion was in the stomach. The median operation time in the successful cases was 18 min, and the average observation time was 67 d. During the observation period, none of the patients experienced any complications associated with OTSC placement. In addition, we successfully used the OTSC to close the perforation site after ESD in 6 patients. This was a single-center, retrospective study with a small sample size. CONCLUSION: The OTSC is effective for treating GI bleeding, fistulae as well as perforations, and the OTSC technique proofed effective treatment for perforation after ESD.

A review on therapeutic potential of Nigella sativa:A miracle herb

Nigella sativa(N.sativa)(Family Ranunculaceae)is a widely used medicinal plant throughout the world.It is very popular in various traditional systems of medicine like Unani and Tibb,Ayurveda and Siddha.Seeds and oil have a long history of folklore usage in various systems of medicines and food.The seeds of N.saliva have been widely used in the treatment of different diseases and ailments.In Islamic literature,it is considered as one of the greatest forms of healing medicine.It has been recommended for using on regular basis in Tibb-e-Nabwi(Prophetic Medicine).It has been widely used as antihypertensive,liver tonics,diuretics,digestive,anti-diarrheal,appetite stimulant,analgesics,anti-bacterial and in skin disorders.Extensive studies on N.sativa have been carried out by various researchers and a wide spectrum of its pharmacological actions have been explored which may include antidiabetic,anticancer,immunomodulator,analgesic,antimicrobial,anti-inflammatory,spasmolytic,bronchodilator,hepato-protective,renal protective,gaslro-prolective,antioxidant properties,etc.Due to its miraculous power of healing,N.sativa has got the place among the top ranked evidence based herbal medicines.This is also revealed that most of the therapeutic,properties of this plant are due to the presence of thymoquinone which is major bioactive component of the essential oil.The present review is an effort to provide a detailed survey of the literature on scientific researches of pharmacognostical characteristics,chemical composition and pharmacological activities of the seeds of this plant.

Human umbilical cord mesenchymal stem cells as treatment of adjuvant rheumatoid arthritis in a rat model

AIM:To investigate the effect of human umbilical cord stem cells,both mesenchymal and hematopoietic(CD34+),in the treatment of arthritis.METHODS:Mesenchymal stem cells(MSCs) and hematopoietic(CD34+) stem cells(HSC) were isolated from human umbilical cord blood obtained from the umbilical cord of healthy pregnant donors undergoing fullterm normal vaginal delivery.MSC,HSC,methotrexate(MTX) and sterile saline were injected intra-articularly into the rat hindpaw with complete freunds adjuvant(CFA) induced arthritis after the onset of disease(day 34),when arthritis had become well established(arthritis score ≥ 2).Arthritic indices were evaluated and the levels of interleukin(IL)-1,tumor necrosis factor(TNF)-α and interferon(IFN)-γ and anti-inflammatory cytokine IL-10 in serum were determined using enzyme-linked immunosorbent assay.Animals of all groups were sacrificed 34 d after beginning treatment,except positive control(PC) which was sacrificed at 10,21 and 34 d for microscopic observation of disease progression.We used hematoxylin,eosin and Masson's trichrome stains for histopathological examination of cartilage and synovium.RESULTS:The mean arthritis scores were similar in all groups at 12 and 34 d post immunization,with no statistical significant difference.Upon the injection of stem cells(hematopoietic and mesenchymal),the overall arthritis signs were significantly improved around 21 d after receiving the injection and totally disappeared at day 34 post treatment in MSC group.Mean hindpaw diameter(mm) in the MSC rats was about half that of the PC and MTX groups(P = 0.007 and P = 0.021,respectively) and 0.6 mm less than the HSC group(P = 0.047),as indicated by paw swelling.Associated with these findings,serum levels of TNF-α,IFN-γ and IL-1 decreased significantly in HSC and MSC groups compared to PC and MTX groups(P < 0.05),while the expression of IL-10 was increased.Histopathological examination with H and E stain revealed that the MTX treated group showed significant reduction of leucocytic infiltrate and hypertrophy of the synovial tissue with moderate obliteration of the joint cavity.Stem cells treated groups(both hematopoietic CD34+ and mesenchymal),showed significant reduction in leucocytic infiltrate and hypertrophy of the synovial tissue with mild obliteration of the joint cavity.With Masson's trichrome,stain sections from the PC group showed evidence of vascular edema of almost all vessels within the synovium in nearly all arthritic rats.Vacuoles were also visible in the outer vessel wall.The vessel became hemorrhagic and finally necrotic.In addition,there was extensive fibrosis completely obliterating the joint cavity.The mean color area percentage of collagen in this group was 0.324 ± 0.096,which was significantly increased when compared to the negative control group.The mean color area percentage of collagen in hematopoietic CD34+ and mesenchymal groups was 0.176 ± 0.0137 and 0.174 ± 0.0197 respectively,which showed a marked decrement compared to the PC group,denoting a mild increase in synovial tissue collagen fibers.CONCLUSION:MSC enhance the efficacy of CFAinduced arthritis treatment,most likely through the modulation of the expression of cytokines and amelioration of pathological changes in joints.

Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats

AIM: To evaluate the role of reactive oxygen species in the pathogenesis of acute ethanol-induced gastric mucosal lesions and the effect of Nigella sativa L oil (NS) and its constituent thymoquinone (TQ) in an experimental model.METHODS: Male Wistar albino rats were assigned into 4groups. Control group was given physiologic saline orally (10 mL/kg body weight) as the vehicle (gavage); ethanol group was administrated 1 mL (per rat) absolute alcohol by gavage; the third and fourth groups were given NS (10 mL/kg body weight) and TQ (10 mg/kg body weight p.o) respectively 1 h prior to alcohol intake. One hour after ethanol administration, stomach tissues were excised for macroscopic examination and biochemical analysis.RESULTS: NS and TQ could protect gastric mucosa against the injurious effect of absolute alcohol and promote ulcer healing as evidenced from the ulcer index (UI) values. NS prevented alcohol-induced increase in thiobarbituric acid-reactive substances (TBARS), an index of lipid peroxidation. NS also increased gastric glutathione content (GSH), enzymatic activities of gastric superoxide dismutase (SOD) and glutathione-S-transferase (GST). Likewise, TQ protected against the ulcerating effect of alcohol and mitigated most of the biochemical adverse effects induced by alcohol in gastric mucosa, but to a lesser extent than NS. Neither NS nor TQ affected catalase activity in gastric tissue.CONCLUSION: Both NS and TQ, particularly NS can partly protect gastric mucosa from acute alcohol-induced mucosal injury, and these gastroprotective effects might be induced, at least partly by their radical scavenging activity.

Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines

AIM: To study the effect of a number of chemotherapeutic drugs on five human intrahepatic cholangiocarcinoma (CCA) cell lines. The expressions of genes that have been proposed to influence the resistance of chemotherapeutic drugs including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), glutathione-S-transferase P1 (GSTP1), multidrug resistance protein (MDR1) and multidrug resistance-associated proteins (MRPs) were also determined.METHODS: Five human CCA cell lines (KKU-100, KKU M055, KKU-M156, KKU-M214 and KKU-OCA17) weretreated with various chemotherapeutic drugs and growth inhibition was determined by 3-(4,5-dimethylthiazol-2-yl)5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Semi-quantitative levels of gene expression were determined by a reverse transcriptase polymerase chain reaction (RT-PCR). Results of IC50 values and the ratios of gene expression were analyzed by linear regression to predict their relationship. RESULTS: Among five CCA cell lines, KKU-M055 was the most sensitive cell line towards all chemotherapeutic drugs investigated, particularly taxane derivatives with IC50 values of 0.02-3 nmol/L, whereas KKU-100 was apparently the least sensitive cell line. When compared to other chemotherapeutic agents, doxorubicin and pirarubicin showed the lowest IC50 values (＜5 μmol/L) in all five CCA cell lines. Results from RT-PCR showed that TS, MRP1, MRP3 and GSTP1 were highly expressed in these five CCA cell lines while DPD and MRP2 were only moderately expressed. It should be noted that MDR1 expression was detected only in KKU-OCA17 cell lines. A strong correlation was only found between the level of MRP3 expression and the IC50 values of etoposide, doxorubicin and pirarubicin (r = 0.86-0.98, ,P＜0.05). CONCLUSION: Sensitivity to chemotherapeutic agents is not associated with the histological type of CCA. Choosing of the appropriate chemotherapeutic regimen for the treatment of CCA requires knowledge of drug sensitivity. MRP3 was correlated with resistance of CCA cell lines to etoposide, doxorubicin and pirarubicin, whereas other chemotherapeutic drugs showed no association. The roleof this multidrug resistance-associated protein, MRP3, in chemotherapeutic resistance in CCA patients needs to be further investigated.

Gene expression profiles in gastric mucosa of sleep deprivation rats

INTRODUCTIONStress has been shown to induce gastric mucosallesions and lower the effectiveness of the mucosa asa barrier.In rats,gastric ulcers can beproduced by cold-restraint stress and it isfrequently employed as a model for the study of themechanisms of stress on ulcer formation.Cold-restraint stress however is not normally

Clinical characteristics and outcome of hepatocellular carcinoma in alcohol related and cryptogenic cirrhosis: a prospective study

BACKGROUND： Non-alcoholic fatty liver disease （NAFLD） is becoming a leading cause of chronic liver disease. Hepato- cellular carcinoma （HCC） is one of its complications. Although the pathophysiology is unclear, it is reasonable to expect that cryptogenic cirrhosis related HCC （cryptogenic HCC） behaves differently to other types of HCC. This study prospectively compared patients with cryptogenic HCC and those with HCC related to alcoholic cirrhosis. METHODS： A total of 150 consecutive patients with HCC （89 cryptogenic HCC and 61 alcohol related HCC） referred to our unit over a 23-month period were studied. Their demographic data, liver function, tumor characteristics and outcomes were compared. RESULTS： Alcohol related HCC was seen only in males. Com- pared with cryptogenic HCC, alcohol related HCC had signifi- cantly higher aspartate aminotransferase/alanine aminotrans- ferase （AST/ALT） ratio （1.7 vs 1.4, P=0.002）, model for end- stage liver disease score （13 vs 11, P=0.018） and Child＇s score （7 vs 6, P=0.037）. No significant difference was seen in platelet counts, serum sodium and AST to platelet ratio index. Single nodular tumors were more common in cryptogenic HCC, while diffuse type tumors and macroscopic vascular invasion were common in alcohol related HCC. In patients who could not be offered any treatment because of advanced tumors or poor liver function, alcohol related HCC had a significantly lower median survival （5.3 months） compared with crypto- genic HCC （9.3 months, P=0.034）.CONCLUSIONS： Compared wtih cryptogenic HCC, alcohol related HCC had worse liver function and aggressive tumor morphology at presentation, and a higher proportion was untreatable. In patients who could not be treated, median sur- vival was lower in patients with alcohol related HCC than in those with cryptogenic HCC.

Exploring dynamic biomedical algorithm of Eurycoma longifolia Jack and its bioactive phytochemicals: A review of pharmacokinetic and pharmacodynamic implications and future prospects

Eurycoma longifolia Jack(E.longifolia) is a well-recognized traditional herbal medicine that offers a wide dynamic range of biomedical applications including anti-osteoporotic, anticancer, anti-proliferative, anti-malarial, antimicrobial, antioxidant, aphrodisiac, antiinflammatory, anxiolytic, anti-diabetic, anti-rheumatism and anti-ulcer properties.This review aims to overview the pharmacokinetic and a pharmacodynamic algorithm of E.longifolia and its bioactive components.Analysis of pharmacokinetic profile revealed that E.longifolia exhibit higher bioavailability, high volume of distribution, slow elimination rate, and does not show inhibitory effects on cytochrome P450 isoenzymes.E.longifolia has been used, alone or in combination with other pharmacological agents, in the form of crude extracts, standard extracts, or decoctions of different plant parts(i.e., herbs, shrubs, stem, leaves, and roots) for the treatment of various ailments in animals and humans.Among various bioactive constituents, eurycomanone has been found to be the most remarkable, super-stable, versatile, and most potent phytochemical(isolated or extracted from root extracts) against various types of animals and human diseases.Based on its well-established pharmacokinetic and pharmacodynamic profiles, we suggested that E.longifolia can be a well-accepted complementary and alternative medicine for the treatment of different types of human ailments.

Difficulty in differentiating two cases of sigmoid stenosis by diverticulitis from cancer

The incidence of colonic diverticulosis with or without diverticulitis has increased in the Japanese population due to the modernization of food and aging.The rate of diverticulitis in colon diverticulosis ranges from 8.1% to 9.6%.However,few cases of stenosis due to diverticulitis have been reported.These reports suggest that the differentiation between sigmoid diverticulitis and colon cancer is difficult.This report describes two cases of colon stenosis due to diverticulitis that were difficult to differentiate from colon cancer.Case 1 was a 70-year-old woman with narrowed stools for 1 month who underwent colonofiberscopy (CFS).CFS revealed a diverticulum and circumferential stenosis in the sigmoid colon.Barium enema revealed a marked,hourglassshaped,2-cm circumferential stenosis in the sigmoid colon.Fluorodeoxyglucose (FDG)-positron emission tomography computed tomography (CT) revealed an increased FDG uptake at the affected portion of the sigmoid colon.Sigmoid colon cancer was suspected,and laparoscopic sigmoidectomy was performed.Pathological examination demonstrated active inflammation with no evidence of malignancy.Case 2 was a 50-yearold man who presented to a nearby clinic with reduced stool output despite the urge to defecate.CFS detected severe stenosis in the sigmoid colon approximately 25 cm from the dentate line.Contrast-enhanced abdominal CT revealed multiple diverticula,wall thickening,and swelling of the lymph nodes around the peritoneal aorta and the inferior mesenteric artery.A partial sigmoidectomy was performed.Pathological examination of the resected specimen revealed no changes in the mucosal epithelial surface,but a marked infiltration of inflammatory cells was observed.

Apoptotic activity of caged xanthones from Garcinia hanburyi in cholangiocarcinoma cell lines

AIM:To investigate the growth inhibitory mechanism of four caged xanthones from Garcinia hanburyi in cholangiocarcinoma(CCA) KKU-100 and KKU-M156 cells.METHODS:Four caged xanthones,selected on the basis of their anticancer potency and chemical structure diversities(i.e.isomorellin,isomorellinol,forbesione and gambogic acid) were used in this study.Growth inhibition of these caged xanthones was determined using the sulforhodamine B assay.Induction of apoptosis was assessed by observing cell morphology,ethidium bromide and acridine orange staining and DNA fragmentation assay.Levels of apoptotic-related gene and protein expressions were determined by a real-time reverse transcriptase polymerase chain reaction and Western blotting analysis,respectively.RESULTS:The compounds were found to inhibit growth of both cell lines in a dose-dependent manner and also showed selective cytotoxicity against the cancer cells when compared with normal peripheral blood mononuclear cells.Growth suppression by these compounds was due to apoptosis,as evidenced by the cell morphological changes,chromatin condensation,nuclear fragmentation,and DNA ladder formation.At the molecular level,these compounds induced down-regulation of Bcl-2 and survivin proteins with up-regulation of Bax and apoptosisinducing factor proteins,leading to the activation of caspase-9 and-3 and DNA fragmentation.The functional group variations did not appear to affect the anticancer activity with regard to the two CCA cell lines;however,at a mechanistic level,isomorellinol exhibited the highest potency in increasing the Bax/Bcl-2 protein expression ratio(120 and 41.4 for KKU-100 and KKU-M156,respectively) and in decreasing survivin protein expression(0.01 fold as compared to control cells in both cell lines).Other activities at the molecular level indicate that functional groups on the prenyl side chain may be important.CONCLUSION:Our findings for the first time demonstrate that four caged xanthones induce apoptosis in CCA cells which is mediated through a mitochondriadependent signaling pathway.

Association between the levels of prostaglandin E2 in tears and severity of dry eye

AIM: To investigate the relationship between the levels of prostaglandin E2(PGE2) in tears and dry eye disease severity based on both clinical symptoms and signs.METHODS: Tear samples were collected from 36 non-Sj?gren syndrome dry eye patients(10 males and 26 females, mean age 50.11±11.17 y). All participants completed the Ocular Surface Disease Index(OSDI) questionnaire and underwent a detailed ophthalmic examination including, tear film breakup time(TBUT), ocular surface fluorescein staining, Schirmer I test, and meibomian gland assessment. The level of PGE2 in tears was measured using enzyme-linked immunosorbent assay(ELISA). The independent associations between tear PGE2 levels and other variables including demographics, OSDI scores, TBUT, Schirmer scores, ocular surface staining scores, and stage of meibomian gland dysfunction(MGD) were evaluated using linear regression analysis. RESULTS: The mean PGE2 level in tears of dry eye patients was 537.85±234.02 pg/mL. The tear PGE2 levels significantly positively correlated with OSDI scores(R=0.608, P<0.001), however, they did not significantly associate with TBUT(R=0.153, P=0.373), Schirmer scores(R=-0.098, P=0.570), ocular surface staining scores(R=0.282, P=0.095), and stage of MGD(R=-0.107, P=0.535).Male sex was significantly negatively correlated with tear PGE2 levels.CONCLUSION: The levels of PGE2 in tears are positively correlated with dry eye symptoms. However, no significant association was found between tear PGE2 levels and the results of other common dry eye diagnostic tests.