Chinese herbal medicine decreases incidence of hepatocellular carcinoma in diabetes mellitus patients with regular insulin management

BACKGROUND Type 2 diabetes mellitus(DM)is an independent risk factor for hepatocellular carcinoma(HCC),while insulin is a potent mitogen.Identifying a new therapeutic modality for preventing insulin users from developing HCC is a critical goal for researchers.AIM To investigate whether regular herbal medicine use can decrease HCC risk in DM patients with regular insulin control.METHODS We used data acquired from the Taiwan,Chinaese National Health Insurance research database between 2000 and 2017.We identified patients with DM who were prescribed insulin for>3 months.The herb user group was further defined as patients prescribed herbal medication for DM for>3 months per annum during RESULTS We initially enrolled 657144 DM patients with regular insulin use from 2000 to 2017.Among these,46849 patients had used a herbal treatment for DM,and 140547 patients were included as the matched control group.The baseline variables were similar between the herb users and nonusers.DM patients with regular herb use had a 12%decreased risk of HCC compared with the control group[adjusted hazard ratio(aHR)=0.88,95%CI=0.80–0.97].The cumulative incidence of HCC in the herb users was significantly lower than that of the nonusers.Patients with a herb use of>5 years cumulatively exhibited a protective effect against development of HCC(aHR=0.82,P<0.05).Of patients who developed HCC,herb users exhibited a longer survival time than nonusers(aHR=0.78,P=0.0001).Additionally,we report the top 10 herbs and formulas in prescriptions and summarize the potential pharmacological effects of the constituents.Our analysis indicated that Astragalus propinquus(Huang Qi)plus Salvia miltiorrhiza Bunge(Dan Shen),and Astragalus propinquus(Huang Qi)plus Trichosanthes kirilowii Maxim.(Tian Hua Fen)were the most frequent combination of single herbs.Meanwhile,Ji Sheng Shen Qi Wan plus Dan Shen was the most frequent combination of herbs and formulas.CONCLUSION This large-scale retrospective cohort study reveals that herbal medicine may decrease HCC risk by 12%in DM patients with regular insulin use.

Beneficial effect of sulphate-bicarbonate-calcium water on gallstone risk and weight control

AIM： To investigate the effect of drinking sulphate-bi- carbonate-calcium thermal water （TW） on risk factors for atherosclerosis and cholesterol gallstone disease.

Recent advances in the managements of type 2 diabetes mellitus and natural hypoglycemic substances

Diabetes has become a global concern at present,among which type 2 diabetes mellitus(T2DM)accounts for approximately 90%-95%of patients.T2DM is a type of metabolic disorder syndrome that results from a genetic defect,and it is based on insulin resistance and an insulin secretion disorder.The occurrence of T2DM is usually the outcome of both genetic and environmental factors and their interactions.The etiology and pathogenesis of diabetes have not been fully elucidated,and no radical therapeutic cure has been found.Patients with T2DM suffer from complications such as the development of a chronic hyperglycemic condition and even serious metabolic disorders and organ damage in the body and depression and dementia,in addition to other chronic complications.Many studies have suggested that diet is crucial in the development of diabetes and the control of blood glucose.Natural substances have the characteristics of low toxicity and few side effects and may be key to the development of diabetic health products and preventive treatments.This paper reviews the etiology,pathogenesis,risks,treatments and diets related to T2DM to summarize the types of recently available natural products,from both local and foreign sources,for lowering blood glucose at home and their application in supplementary hypoglycemic foods.The key findings and conclusions suggest that there are various known T2DM-inducing factors,including genetic and environmental factors and three types of hybrid factors.

Potential roles of longan flower and seed extracts for anticancer

Polyphenol-rich plants are known to possess benefits to human health. Recent studies have revealed that many Traditional Chinese Medicines(TCMs) are rich sources of polyphenols and exhibit antioxidant and anti-inflammatory activities, and these TCMs have been shown experimentally to overcome some chronic diseases, including cancer. Longan flowers and seeds, two TCMs traditionally used for relieving pain and urinary diseases, have been revealed in our recent reports and other studies to possess rich amounts of polyphenolic species and exhibit strong anti-oxidant activity, and these could be applied for the treatment of diabetes and cancer. Herein, we review the recent findings regarding the benefits of these two TCMs in the treatment of humancancer and the possible cellular and molecular mechanisms of both substances.

Effects of Klebsiella pneumoniae on Toll-Like Receptor-Dependent Endoplasmic Reticulum Stress-Related Signaling Pathways and Gene Expression and Promotes HLA-B27 Misfolding

Klebsiella has been considered as initiator of AS （ankylosing spondylitis） for nearly four decades. This study aimed to demonstrate that Klebsiella triggers ERS （endoplasmic reticulum stress） and HLA-B27 heavy chain misfolding. CA46 cells or splenocytes obtained from wild-type, MyD88/ or TLR9/ mice were stimulated with KP （Klebsiella pneumoniae） or its components including CPS （capsule polysaccharide）, LPS （lipopolysaccharide）, and KP gDNA （genomic deoxyribonucleic acid） respectively for 24 h and 48 h. The activation of ERS-related signaling was detected by Western blotting or RT-PCR, and the level of misfolded HLA-B27 was determined by non-reducing protein gel electrophoresis and Western blotting. The protein expression of BiP/Grp78 and calreticulin, the alternative splicing of XBP-1 mRNA （messenger ribonucleic acid）, and the activation of caspase-12 and p38 were increased in a dose-dependent manner in HLA-B27-expressing CA46 cells after treatment with decapsulated KP. We also demonstrate that the EP, S-inducing effects occur via the TLR （Toll-like receptor）/MyD88-dependent signaling pathway. Significantly, HLA-B27 misfolding was also detected in decapsulated KP-treated B27-expressing cells. These results suggest that the non-antigen-specific induction of ERS and B27 misfoiding through TLR/MyD88 signaling might promote KP antigen-initiated autoreactive responses via the presentation of misfolded B27, and that small-molecules targeting TLRs might have potential as novel therapeutic agents for AS.

Peptide-based enteral formula improves tolerance and clinical outcomes in abdominal surgery patients relative to a whole protein enteral formula

AIM To compare a dipeptide- and tripeptide-based enteral formula with a standard enteral formula for tolerance and nutritional outcomes in abdominal surgery patients.METHODS A retrospective study was performed to assess the differences between a whole-protein formula(WPF) and a dipeptide- and tripeptide-based formula(PEF) in clinical outcomes.Seventy-two adult intensive care unit(ICU) patients with serum albumin concentrations less than 3.0 g/d L were enrolled in this study.Patients were divided into two groups(WPF group = 40 patients,PEF group = 32 patients).The study patients were fed for at least 7 d,with ≥ 1000 m L of enteral formula infused on at least 3 of the days.RESULTS The mean serum albumin level on postoperative day(POD) 10,prealbumin levels on POD-5 and POD-10,and total lymphocyte count on POD-5 were significantly higher in the PEF group compared to those in the WPF group(P < 0.05).The average maximum gastric residual volume of the PEF patients during their ICU stays was significantly lower than that for WPF patients.CONCLUSION Dipeptide- and tripeptide-based enteral formulas are more efficacious and better tolerated than wholeprotein formulas.

Helicobacter pylori infection in obesity and its clinical outcome after bariatric surgery

The present review summarizes the prevalence and active clinical problems in obese patients with Helicobacter pylori(H.pylori)infection,as well as the outcomes after bariatric surgery in this patient population.The involvement of H.pylori in the pathophysiology of obesity is still debated.It may be that the infection is protective against obesity,because of the gastritis-induced decrease in production and secretion of the orexigenic hormone ghrelin.However,recent epidemiological studies have failed to show an association between H.pylori infection and reduced body mass index.H.pylori infection might represent a limiting factor in the access to bariatric bypass surgery,even if highquality evidence indicating the advantages of preoperative H.pylori screening and eradication is lacking.The clinical management of infection is complicated by the lower eradication rates with standard therapeutic regimens reported in obese patients than in the normalweight population.Prospective clinical studies to ameliorate both H.pylori eradication rates and control the clinical outcomes of H.pylori infection after different bariatric procedures are warranted.

Dynamics of cytokines predicts risk of hepatocellular carcinoma among chronic hepatitis C patients after viral eradication

BACKGROUND Chronic hepatitis C virus(HCV)infection induces profound alterations in the cytokine and chemokine signatures in peripheral blood.Clearance of HCV by antivirals results in host immune modification,which may interfere with immune-mediated cancer surveillance.Identifying HCV patients who remain at risk of hepatocellular carcinoma(HCC)following HCV eradication remains an unmet need.We hypothesized that antiviral therapy-induced immune reconstruction may be relevant to HCC development.AIM To investigate the impact of differential dynamics of cytokine expression on the development of HCC following successful antiviral therapy.METHODS One hundred treatment-naïve HCV patients with advanced fibrosis(F3/4)treated with direct-acting antivirals(DAAs)or peginterferon/ribavirin who achieved sustained virologic response[SVR,defined as undetectable HCV RNA throughout 12 wk(SVR12)for the DAA group or 24 wk(SVR24)for the interferon group after completion of antiviral therapy]were enrolled since 2003.The primary endpoint was the development of new-onset HCC.Standard HCC surveillance(abdominal ultrasound andα-fetoprotein)was performed every six months during the followup.Overall,64 serum cytokines were detected by the multiplex immunoassay at baseline and 24 wk after end-of-treatment.RESULTS HCC developed in 12 of the 97 patients over 459 person-years after HCV eradication.In univariate analysis,the Fibrosis-4 index(FIB-4),hemoglobin A1c(HbA1c),the dynamics of tumor necrosis factor-α(TNF-α),and TNF-like weak inducer of apoptosis(TWEAK)after antiviral therapy were significant HCC predictors.The multivariate Cox regression model showed thatΔTNF-α(≤-5.7 pg/mL)was the most important risk factor for HCC(HR=11.54,95%CI:2.27-58.72,P=0.003 in overall cases;HR=9.98,95%CI:1.88-52.87,P=0.007 in the interferon group).An HCC predictive model comprising FIB-4,HbA1c,ΔTNF-α,andΔTWEAK had excellent performance,with 3-,5-,10-,and 13-year areas under the curve of 0.882,0.864,0.903,and 1.000,respectively.The 5-year accumulative risks of HCC were 0%,16.9%,and 40.0%in the low-,intermediate-,and high-risk groups,respectively.CONCLUSION Downregulation of serum TNF-αsignificantly increases the risk of HCC after HCV eradication.A predictive model consisting of cytokine kinetics could ameliorate personalized HCC surveillance strategies for post-SVR HCV patients.

Anti-cancer potential of litchi seed extract

Polyphenol-rich fruit are believed to be healthy food for humans. Traditional Chinese Medicines(TCMs) from fruit are rich sources of polyphenols and exhibit antioxidant and anti-inflammatory activities, and have been shown experimentally to overcome some chronic diseases, including cancer. The litchi seed is one of the TCMs traditionally used for relieving pain and sweating, and has been revealed in our recent report and other studies to possess rich amounts of polyphenolic species, including flavonoids and proanthocyanidines, and exhibits strong anti-oxidant activity, and could be applied for the treatment of diabetes and cancer. Herein, we review the recent findings regarding the benefits of this TCM in the treatment of human cancer and the possible cellular and molecular mechanisms of the litchi seed.

Pharmarcogenetic Mechanism of ACE liD Polymorphism Adversely Responding to ACE Inhibitors in Regulating the ACE Promoter Activity in Neurons

The ACE （angiotensin converting enzyme） inhibitors are not only drugs widely prescribed drugs in cardiovascular diseases, but also potentially therapeutic agents in dementia. Based on the findings that the ACE inhibitors could activate the c-Jun N-terminal kinase signal to increase the ACE gene expression and that the Alu element of the human ACE gene involved in regulating ACE promoter activity, we aimed to investigate whether there are different pharmacogenetic responses of ACE I/D polymorphism to the ACE inhibitors in neurons. The three reporter vectors, pACEpro（0-SEAP, p-I-ACEpro-SEAP, and p-D-ACEpro-SEAP were used to examine the transcriptional activity of the vectors responding to the lisinopril treatment using a transient-transfection method in SH-SY5Y cells. Our results showed that lisinopril increased the promoter activity of an ACE gene by 16.7%. Additionally, we found the lisinopril enhanced the ACE promoter activity of the I-form vector by 17.2%, but adversely reduced that of the D-form vector by 16.8%, as compared with the respective control without the lisinopril treatment. Firstly, our findings had proved that the UD polymorphism of ACE gene contrarily responds to the ACE inhibitors in regulating the ACE expression in neurons, which provide a novel insight suggesting genetic testing to tailor the treatment regimens in AD （Alzheimer＇s disease） patients.

Predictive role of XRCC5/XRCC6 genotypes in digestive system cancers

Cancers are a worldwide concern;oral,esophageal and gastrointestinal cancers represent important causes of cancer-related mortality and contribute to a signif icant burden of human health.The DNA repair systems are the genome caretakers,playing a critical role in the initiation and progression of cancers.However,the association between the genomic variations of DNA repair genes and cancer susceptibility is not well understood.This review focuses on the polymorphic genotypes of the non-homologous end-joining DNA repair system,highlighting the role of two genes of this pathway,XRCC5 and XRCC6,in the susceptibility to digestive system cancers and discussing their potential contributions to personalized medicine.

Does <i>Culicoides</i>spp. (Diptera: Ceratopogonidae) Not Suck Human Blood in Riparian Habitat of a National Park

Is the wild animal conservation result in Taiwan good enough to provide the blood resources for the blood sucking insect and cause the insect behavior changed? Based on the bimonthly investigation of Culicoides sp. in Wuling area, Sheipar National Park, by both human bait method and light trap method, we found that there were totally 13,191 individuals trapped by light trap and collected but no one single Culicoides sp. trapped by human bait during the study period of Wuling Long Term Ecological Research (WLTER) in 2012. Two of the three sites were recorded and reported as the midge attacked the ranger and tourists of Sheipa National Park in 2010 and 2011 respectively. Along with the study of WLTER some wild animals encounter more often than before, especially the bird population in the riparian ecosystem of the mountain river Chi Chia Wan Stream. On the other end, Culicoides sp. preferred to the blood of birds and amphibians as well as mammals according to the article review. So, the effectiveness of blood resource from wild animals may cause the behavior of blood sucking insect like as Culicoides sp. shifted to or returned back to the original and the favorite blood resource.

Different Mechanisms of Seed Kernel Extract from <i>Mangifera indica</i>on the Growth of Two Colon Cancer Cell Lines

Flesh extract of Mangifera indica possesses anti-proliferation effect on different types of cancer cells. However, the effect of its seed kernel extract (MSP) on the growth of human colorectal carcinoma cells (CRC) has not yet been evaluated. Phenolic species of MSP were extracted and measured by colorimetry. Two CRC cell lines (Colo 320DM and SW480) were treated with MSP and assessed for viability by trypan blue exclusion, for cell cycle distribution by flow cytometry, for apoptosis by annexin V labeling, for mitochondria potential by rhodamine 123 staining and for changes in the levels of proteins involved in cell cycle control or apoptosis by immunoblotting. MSP inhibited the proliferation (12.5 μg/mL - 50 μg/mL) of Colo 320DM and SW480. MSP inhibited proliferation by blocking cell cycle progression at G1 (SW480) or S (Colo 320DM) phase and inducing apoptotic death. Western blotting indicated that MSP-blocking cell cycle was associated with cyclin levels. MSP-treated Colo 320DM and SW480 also showed activation of caspase 8, 9 and 3. MSP induces cell cycle arrest and apoptotic death in two CRC cell lines. The results indicate that MSP is a potential novel chemoprevention and treatment agent for colorectal cancer.

Therapeutic Potential of the Medicinal Plant Tinospora cordifolia–Minireview

For thousands of years,plant based herbal medicines have been utilized by millions of people all over the world.Plant materials or products are used in different folk/traditional medical systems,such as the Chinese,African and Indian medical systems,like Siddha,Ayurveda,Unani,and Homeopathy.Tinospora cordifolia(TC)is a medicinal plant belonging to the family Menispermaceae.It is a big deciduous,climbing shrub growing prevalently in the tropical part of Indian subcontinent regions such as India,Pakistan,Nepal,Bhutan,Bangladesh and Srilanka,and in Myanmar,and China.Guduchi,Giloy,Shindilkodi,and Amritha are all the common names for this plant.Extracts from different parts of this herbal plant have been used to treat many diseases.In Ayurvedic medicine,extract from this plant is used for preparing“rasayanas”,which is known to cure diabetes,skin diseases,allergic conditions,jaundice,cardiovascular diseases,rheumatoid arthritis,poisoning,and microbial infections.T.cordifolia has a many bioactive phytochemicals that have been isolated from its aerial parts and roots.Many bioactive principles have been reported from this plant which belong to various classes like alkaloids,aliphatic compounds,diterpenoid lactones,phenolics,flavonoids,glycosides,sesquiterpenoids,lignans,steroids and polysaccharides.T.cordifolia possesses medicinal properties such as antioxidant,antiallergic,antiinflammatory,antimicrobial,antiviral,antidote,antitumor,antileprotic,antispasmodic,and antidiabetic properties.The present review will provide a comprehensive therapeutic potential of T.cordifolia.

Effect of berberine on activity and mRNA expression of N-acetyl transferase in human lung cancer cell line A549

OBJECTIVE： To study the effects of berberine on ac- tivity and mRNA expression of N-acetyltransferase in human lung cancer cell line A549. METHODS： N-acetyltransferase antibodies wereprepared. The human lung cancer A549 cells were cultivated randomly in the wells of culture plate, and divided into the control group, and berberine 0.0008, 0.008, 0.08, 0.8 and 1.6 mM treatment groups, with 3 wells for each group. 24 h later, A549 cells in each group were collected respectively, the content of N-acetyltransferase was detected by Flow cytometry, and the mRNA expression of N-acetyltransferase was observed by reverse tran- scription polymerase chain reaction. RESULTS The N-acetyltransferase content in hu- man lung cancer A549 cells decreased with the in- creasing of berberine concentration, significantly lower than that in the control group （P〈O.05 or P〈 0.001）; and the mRNA expression of N-acetyltrans- ferase also decreased with the increasing of berber- ine concentration, significantly lower in Huanglian- su treatment groups （P〈0.O01）. CONCLUSION： Berberine can inhibit the activity of N-acetyltransferase in human lung cancer cell line A549, and shows negative correlations of dose and time in a certain extent. The inhibited gene expres- sion of N-acetyltransferase in human lung cancer A549 cell may probably represent one of the mech- anisms for its antineoplastic effect.

Comparisons of Subjective and Objective Measures of Free-Living Daily Physical Activity and Sedentary Behavior in College Students

Purpose To compare physical activity and sedentary behavior between four commonly used subjective and objective meas-ures:the 7-day Physical Activity Recall (7DPAR),International Physical Activity Questionnaire (IPAQ),pedometer,and accelerometer.Methods A total of 130 college students completed four measures for the same 7 days.Body composition was measured using a bioelectric impedance analyzer.Wilcoxon signed rank tests and Spearman correlations were performed to compare estimates between activity measures.The Spearman correlations between different activity measures were further examined separately for the higher and the lower body fat groups.Results Compared with accelerometer-derived data,both the 7DPAR and the IPAQ overestimated light physical activity(P < 0.001) while underestimated sedentary behavior (P < 0.001).Across comparisons,the highest correlation was found between accelerometers and pedometers on steps/day (r =0.72,P < 0.001).The 7DPAR and the IPAQ were correlated with each other for all physical activity variables and sedentary behavior (r =0.37-0.45).There were low correlations (r=0.20-0.47) between the 7DPAR,the IPAQ,and accelerometers in sedentary behavior,light physical activity,and vigorous physical activity.Higher correlations between different activity modalities were observed among individuals with lower body fat(r=0.41-0.80) than among those with higher body fat (r=0.31-0.65).Conclusions The 7DPAR and the IPAQ yielded comparable estimation of moderate physical activity relative to accelerom-eters.There were significant differences in sedentary time across activity measures.Body compositions should be considered when comparing the estimates of activity levels between subjective and objective instruments.

Is the role of the angiotensin-converting enzyme gene in Alzheimer's disease independent of hypertension?

Objective: Angiotensin-converting enzyme(ACE) insertion/deletion(I/D) polymorphisms are considered biomarkers of late-onset Alzheimer's disease(AD). However, the results of studies of these polymorphisms have been inconsistent. The ACE protein directly degrades beta-amyloid and thereby slows the progression of AD and its onset. However, it also activates the renin–angiotensin–aldosterone system, which can contribute to hypertension and/or cardiovascular events that increase the risk for developing AD. Methods: In this study, we examined the bidirectional association of the ACE gene and AD in patients with AD with and without hypertension. Results: Patients who were clinically diagnosed with AD(n = 983) underwent ACE I/D genotyping. The distribution of the ACE I/D genotypes(P = 0.355 for I/I vs. D/D; P = 0.888 for I/D vs. D/D) and I alleles(P = 0.895) did not significantly differ between hypertensive patients with AD and patients with AD without hypertension. Conclusions: In contrast to traditional theories, the results of this study suggested that the contribution of the ACE gene to the development of AD was not associated with hypertension and similar cardiovascular effects.