Mechanism of anticancer effect of gambogic acid on gastric signet ring cell carcinoma.

Gambogic acid has demonstrated inhibitory effects on the growth of various cancer cell types, such as breast cancer, pancreatic cancer, prostate cancer, lung cancer, and osteosarcoma. This study aims to investigate the antiproliferative activity of Gambogic acid on SNU-16 cells derived from gastric signet ring cell carcinoma and elucidate the underlying mechanisms. The cytotoxic effect of gambogic acid was evaluated in SNU-16 cells by treating them with different concentrations of the compound, and the XTT cell viability assay was employed to assess cell viability. ELISA was used to measure bax, BCL-2, caspase 3, PARP, and 8-oxo-dG levels. Additionally, immunofluorescence staining was applied to assess 8-oxo-dG and LC3ß levels in SNU-16 cells. It was observed that gambogic acid exerted a dose-dependent and statistically significant antiproliferative effect on SNU-16 cells. The IC50 value of gambogic acid in SNU-16 cells was found to be 655.1 nM for 24 h. Subsequent investigations conducted using the IC50 dose revealed a significant upregulation of apoptotic proteins including cleaved caspase 3, Bax, and cleaved PARP (p < 0.001), along with a downregulation of BCL-2 (p < 0.001), an anti-apoptotic protein. Moreover, the administration of this drug led to an upregulation of 8-oxo-dG (p < 0.001), a widely acknowledged biomarker indicating oxidative damage in DNA, as well as an increase in LC3ß levels (p < 0.05), a marker associated with autophagy. The antiproliferative effect of gambogic acid against gastric signet ring cell carcinoma is attributed to its ability to induce apoptosis and autophagy. This discovery highlights the promising potential of gambogic acid as a treatment option for gastric signet ring cell carcinoma.

Anticancer activity of sinapic acid by inducing apoptosis in HT-29 human colon cancer cell line.

Colorectal cancer is the third most lethal and fourth most commonly diagnosed cancer worldwide. Sinapic acid, a derivative of hydroxycinnamic acid, is a promising phytochemical exhibiting numerous pharmacological activities in various systems. It is a substantial chain-breaking antioxidant that operates as a radical scavenger. The aim of this research was to investigate the antiproliferative effect of sinapic acid on the HT-29 cell line besides the mechanisms underlying this activity. The effect of sinapic acid on the viability of HT-29 cell line was investigated using XTT assay. The levels of BCL-2, cleaved caspase 3, BAX, cleaved PARP, and 8-oxo-dG were measured using ELISA. Gamma-H2AX and cytochrome c expressions were assessed semiquantitatively using immunofluorescence staining. Sinapic acid at 200 µm and higher doses produced a significant antiproliferative effect on HT-29 cells. The IC50 value was found to be 317.5 µm for 24 h. Sinapic acid (317.5 µm) significantly elevated cleaved caspase 3, BAX, cleaved PARP, and 8-oxo-dG levels. The levels of gamma-H2AX foci are significantly higher, while the levels of cytochrome c are lower in sinapic acid-treated HT-29 cells. These results indicate that sinapic acid has antiproliferative, apoptotic, and genotoxic effects on colon cancer cells.

Galium aparine L. protects against acetaminophen-induced hepatotoxicity in rats.

The toxicity of acetaminophen (N-acetyl-para-aminophenol (APAP)) is the most frequent cause of drug-induced liver damage. Galium aparine L. (GA) is traditionally used to treat jaundice. We aimed to investigate the hepatoprotective potential of GA in the APAP-induced hepatic encephalopathy (HE) rat model. Qualitative phytochemical characterization of GA was performed by LC/Q-TOF/MS analysis. Wistar rats were pretreated with GA (250 and 500 mg/kg b.wt. per oral) for five days. On the 6th day, the rats were exposed to APAP (1500 mg/kg b.wt. oral gavage) and behavioral tests (open field and passive avoidance tests) were applied on the 7th and 8th days. The animals were killed, and biochemical and histopathological parameters were assessed in blood and hepatic specimens. GA pretreated rats exhibited a significant reduction in APAP-induced liver damage, evidenced by the reduction in liver necrosis and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin (BIL). GA demonstrated an anxiolytic effect, as seen in the acquisition trial and grooming behavior. The short-term memory performances of animals were not changed in all groups, suggesting that APAP intoxication did not affect hippocampal function. These results show that GA extract markedly exerts hepatoprotective activity, while its effect on hepatic encephalopathy was limited.

New anti-viral drugs for the treatment of COVID-19 instead of favipiravir.

The SARS-CoV-2 virus is a major problem in the world right now. Currently, all the attention of research centers and governments globally are focused on the investigation of vaccination studies and the discovery of small molecules that inhibit the SARS-CoV-2 virus in the treatment of patients. The goal of this study was to locate small molecules to be used against COVID19 instead of favipiravir. Favipiravir analogues were selected as drug candidates from the PubChem web tool. The RNA dependent RNA polymerase (RdRp) protein was selected as the target protein as favipiravir inhibits this protein in the human body. Initially, the inhibition activity of the studied compounds against RdRp of different virus types was investigated. Then, the inhibition properties of selected drug candidates and favipiravir were examined in detail against SARS-CoV-2 RdRp proteins. It was found that 2-oxo-1H-pyrazine-3-carboxamide performed better than favipiravir in the results of molecular docking, molecular mechanics Poisson-Boltzmann surface area (MM-PSBA) calculations, and ADME analyses.Communicated by Ramaswamy H. Sarma.

Is it possible to use Proton Pump Inhibitors in COVID-19 treatment and prophylaxis?

Coronaviruses (CoV), discovered after 1960, caused human life-threatening outbreaks. SARS-CoV2, which appeared in Wuhan, China in December 2019, causing Severe Acute Respiratory Syndrome and has different features than other coronaviruses, has been determined and the disease caused by the virus has been called "Coronavirus Disease-2019" (COVID-19). This disease activates both the natural and acquired immune system. The cytokin storm, in which blood levels of proinflammatory cytokines are detected excessively high is developing and the uncontrolled inflammatory response causes local and systemic tissue damages. Although a spesific drug has not been found yet, the medications currently in use for other indications, whose pharmacokinetic- pharmacodynamic properties and toxic doses are already known; are included in the treatment practice of COVID-19. These drugs affect the entry of the virus into the cell and its intracellular distribution. They also have anti-inflammatory and immunomodulating effects too. Therefore, we think that Proton Pump Inhibitors (PPI's) with similar mechanisms of action may also be involved in COVID-19 treatment and prophylaxis.

Comparative Relaxant Effects of Ataciguat and Zaprinast on Sheep Sphincter of Oddi.

BACKGROUND: Relaxing the sphincter of Oddi (SO) is an important process during endoscopic retrograde cholangiopancreatography (ERCP) procedures. This issue suggests that the easier the sphincterotomy and cannulation, the more post-ERCP complications decrease. AIMS: To compare the relaxant effects of ataciguat (a novel soluble guanylyl cyclase activator) and zaprinast (an inhibitor of phosphodiesterase 5) on sheep SO in vitro, thus testing whether they can be used during ERCP. STUDY DESIGN: Animal experimentation. METHODS: Sheep SO rings were placed in tissue baths and their isometric tension to ataciguat and zaprinast were tested. We also tested their isometric tension against ataciguat in the presence of 1H-(1,2,4) oxadiazole (4,3-a) quinoxalin-1-one (ODQ) which is a soluble guanylyl cyclase inhibitor. RESULTS: Ataciguat and zaprinast both triggered concentration addicted relaxation on sheep SO rings (p=0.0018, p=0.0025 respectively) but the relaxation of the ataciguat was significantly greater than that of zaprinast at all concentrations (p=0.0024). It was observed that decreased relaxation responses were initiated by ataciguat in the presence of ODQ (p=0.0012). CONCLUSION: Ataciguat and zaprinast both have relaxing effects on sphincter of Oddi, although that of zaprinast is lower. We believe that ataciguat and zaprinast can be used in ERCP procedures in order to relax the sphincter of Oddi and thus can be used locally in order to decrease complications.

Effects of a Multikinase Inhibitor Motesanib (AMG 706) Alone and Combined with the Selective DuP-697 COX-2 Inhibitor on Colorectal Cancer Cells.

In the present study, we investigated the effects of motesanib (AMG 706), a multikinase inhibitor alone and in combination with DuP-697, an irreversible selective inhibitor of COX-2, on cell proliferation, angiogenesis, and apoptosis induction in a human colorectal cancer cell line (HT29). Real time cell analysis (RTCA, Xcelligence system) was used to determine the effects on colorectal cancer cell proliferation. Apoptosis was assessed with annexin V staining and angiogenesis was determined with chorioallantoic membrane model. We found that motesanib alone exerted antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. Combination with DUP-697 increased the antiproliferative, antiangiogenic and apoptotic effects. Results of this study indicate that motesanib may be a good choice in treatment of colorectal tumors. In addition, the increased effects of combination of motesanib with DuP-697 raise the possibility of using lower doses of these drugs and therefore avoid/minimize the dose-dependent side effects generally observed.

What is hippotherapy? The indications and effectiveness of hippotherapy.

Hippotherapy is a form of physical, occupational and speech therapy in which a therapist uses the characteristic movements of a horse to provide carefully graded motor and sensory input. A foundation is established to improve neurological function and sensory processing, which can be generalized to a wide range of daily activities. Unlike therapeutic horseback riding (where specific riding skills are taught), the movement of the horse is a means to a treatment goal when utilizing hippotherapy as a treatment strategy. Hippotherapy has been used to treat patients with neurological or other disabilities, such as autism, cerebral palsy, arthritis, multiple sclerosis, head injury, stroke, spinal cord injury, behavioral disorders and psychiatric disorders. The effectiveness of hippotherapy for many of these indications is unclear, and more research has been needed. Here, we purpose to give information about hippotherapy which is not known adequately by many clinicians and health workers.

Strontium chloride: can it be a new treatment option for ulcerative colitis?

BACKGROUND/AIMS: Patients with ulcerative colitis still need effective therapy without major side effects. It has been found that strontium can suppress NFκB activation induced by TNF-α. This opens a gate to a new anti-TNF agent which is cheap and can be given orally. We for the first time aimed to investigate the effect of strontium chloride (SrCl2) on inflammation in experimental colitis. METHODS: Thirty female Wistar albino rats were divided into 5 groups each containing 6 rats. The rats in groups 1 and 2 served as the healthy control and colitis group, respectively. The rats in groups 3, 4, and 5 had colitis and received 40 mg/kg SrCl2, 160 mg/kg SrCl2, and 1 mg/kg prednisolone by oral gavage, respectively. The rats were sacrificed for histological evaluation and determination of serum neopterin, TNF-α, and IFN-γ levels. RESULTS: The neopterin, TNF-α and IFNγ levels of group 2 was significantly higher than the other groups. The neopterin, TNF-α, and IFN-γ levels of controls and other treatment groups were comparable. There were a significant difference in macroscopic and microscopic healing between group 2 and other groups histologically. But there was not a significant difference within treatment receiving groups. CONCLUSION: SrCl2 had comparable therapeutic efficiency with prednisolone.

Does mean platelet volume influence the attack or attack-free period in the patients with Familial Mediterranean fever?

Familial Mediterranean fever (FMF) is an autosomal recessive hereditary disease which is characterized by recurrent attacks of fever and peritonitis, pleuritis, arthritis, or erysipelas-like skin disease. Mean platelet volume (MPV) is a sign of platelet activation. There are limited studies in the literature about MPV levels in FMF patients. We aimed to investigate MPV levels during the attack period (group 1) and attack-free periods (group 2) in FMF patients, and to compare them with healthy controls (group 3). The study consisted of the data of: 60 group 1 patients, 120 group 2 patients, and 75 group 3 patients. Erythrocyte sedimentation rate, C-reactive protein, white blood cell count, platelet count, and MPV levels were retrospectively recorded from patient files. Statistical analyses showed that MPV was significantly lower in FMF patients both in group 1 and group 2 than in group 3 (p = 0.004, p = 0.002, respectively); however, there was no difference among group 1 and group 2 in patients with FMF (p = 0.279). The mean platelet count of group 1 was higher than that of group 3 (p = 0.010). In conclusion, this study results suggested that MPV level did not increase on the contrary, it decreased in patients with FMF both in group 1 and/or group 2 when compared to group 3. It was concluded that the lower MPV level was an expected result of secondary thrombocytosis in FMF patients.

Long-term efficacy and safety of lamivudine, entecavir, and tenofovir for treatment of hepatitis B virus-related cirrhosis.

BACKGROUND & AIMS: Data are limited on the efficacy and safety of tenofovir and entecavir when given for more than 1 year to patients with hepatitis B-related cirrhosis. We investigated the long-term safety and efficacy of these antiviral drugs in patients with chronic hepatitis B virus (HBV) infection, with compensated or decompensated cirrhosis, and compared results with those from lamivudine. METHODS: We performed a retrospective analysis of data from 227 adult patients with chronic HBV infection who were diagnosed with cirrhosis, beginning in 2005, at 18 centers throughout Turkey. There were 104 patients who had decompensated cirrhosis, and 197 patients were treatment naive before. Seventy-two patients received tenofovir (followed up for 21.4 ± 9.7 mo), 77 patients received entecavir (followed up for 24.0 ± 13.3 mo), and 74 patients received lamivudine (followed up for 36.5 ± 24.1 mo). We collected data on patient demographics and baseline characteristics. Laboratory test results, clinical outcomes, and drug-related adverse events were compared among groups. RESULTS: Levels of HBV DNA less than 400 copies/mL were achieved in 91.5%, 92.5%, and 77% of patients receiving tenofovir, entecavir, or lamivudine, respectively. Levels of alanine aminotransferase normalized in 86.8%, 92.1%, and 71.8% of patients who received tenofovir, entecavir, and lamivudine, respectively. Child-Turcotte-Pugh scores increased among 8.5% of patients who received tenofovir, 15.6% who received entecavir, and 27.4% who received lamivudine. Frequencies of complications from cirrhosis, including hepatic encephalopathy, variceal bleeding, hepatocellular carcinoma, and mortality, were similar among groups. Lamivudine had to be changed to another drug for 32.4% of the patients. CONCLUSIONS: Tenofovir and entecavir are effective and safe for long-term use in patients with compensated or decompensated cirrhosis from HBV infection.

Peripheral arthritis in the course of inflammatory bowel diseases.

BACKGROUND: Musculoskeletal disorders are well-defined extra-intestinal manifestations of inflammatory bowel diseases (IBD). There is little data regarding the frequencies of IBD and extra-intestinal manifestations from Central and East Europe and Middle Eastern countries. AIMS: To determine the prevalence of peripheral arthritis in IBD and to document the relationship to other extra-intestinal manifestations. METHODS: Enrolled in the study were 357 patients who were diagnosed with IBD from December 2002 through January 2008. All of the patients underwent a detailed whole-body examination by a gastroenterologist and rheumatologist. RESULTS: IBD-related peripheral arthritis (IBDPA) was found in 66 (18.5%) of the 357 patients (28.3% Crohn's disease, 13.5% ulcerative colitis; p=0.001 χ=11.62). IBDPA was more frequent in female patients (60.6 vs. 39.4%, p=0.000, χ=11.12). In eight (12.1%) cases, IBDPA occurred before the onset of IBD. Acute self-limiting episodes, recurrences of the attacks, and persistent symptoms of arthritis were present in 40 (60.6%), 26 (39.3%), and 29 (45.7%) patients, respectively. Arthritis was symmetrical in 33 (50%) cases. Knees (65.2%) and ankles (62.1%) were the most commonly affected joints. Erythema nodosum and pyoderma gangrenosum were more common among patients with IBDPA than patients without it (p=0.001, χ=10.49, and p=0.000 χ=25.77, respectively). CONCLUSIONS: IBDPA is a frequent extra-intestinal complication of IBD. Those of female gender and the presence of Crohn's disease, erythema nodosum and pyoderma gangrenosum have a higher risk to develop IBDPA.

Fatal rhinocerebral mucormycosis under the shade of hepatic encephalopathy.

Mucormycosis is an acutely fatal infection that occurs in immuncompromised patients. Cirrhosis is an acquired immune deficiency state and those patients are more prone to develop opportunistic infections. A 42-years-old cirrhotic man was admitted to our gastroenterology clinic with hepatic encephalopathy. Although he recovered from encephalopathy with supportive measurements, he developed paresthesia on the face. He was diagnosed with rhinocerebral mucormycosis and antifungal therapy was administered. Surgical treatment couldn.t be performed because of his bleeding diathesis and poor general condition. He succumbed on the 12th day of his admission.

Effect of sequential treatment as a first-line therapy for Helicobacter pylori eradication in patients with diabetes mellitus.

OBJECTIVES: The Maastricht III Consensus agreed that effective treatment for Helicobacter pylori (HP) should achieve an intention-to-treat (ITT) eradication rate above 80%, which is still lacking in patients with type 2 diabetes mellitus (DM). This pilot study was designed to confirm the efficacy of a 14-day sequential treatment regimen in patients with type 2 DM. METHODS: This is a prospective, open-label, single-center pilot study. All patients included in this study underwent upper gastrointestinal endoscopy. HP status was evaluated in each patient by a rapid urease test and histopathologic examination. For seven days, all patients received pantoprazole 40 mg twice daily (b.i.d.) and amoxicillin 1000 mg b.i.d., followed by pantoprazole 40 mg b.i.d., metronidazole 500 mg b.i.d., and tetracycline 500 mg four times per day (q.i.d.) [DOSAGE ERROR CORRECTED] for the remaining seven days. The study population consisted of 38 consecutive patients with type 2 DM (18 female, 20 male; mean age 48.0 ± 12.2 years), 30 of whom had non-ulcer dyspepsia, four had gastritis, one had gastric ulcer, and three had duodenal ulcer disease. Eradication was defined as the absence of HP as assessed with the 14C-urea breath test. RESULTS: Thirty-seven of 38 patients completed the study. All side effects were observed in eight patients (21.1%). None of the patients discontinued treatment because of side effects. The eradication rate in the DM group was 22/38 (57.9%) for the ITT analysis and 22/37 (59.5%) for the per-protocol (PP) analysis. CONCLUSION: The results of 14-day sequential therapy for the first-line treatment of HP in patients with type 2 DM were disappointing. Further studies with new antibiotic combinations are needed to find better methods of eradicating HP in patients with type 2 DM.

A new variant of bile duct duplication with coexistence of distal cholangiocarcinoma.

BACKGROUND: A 72-year-old hypertensive woman presented with a 2-month history of right upper quadrant abdominal pain. She had a 15-day history of jaundice, fever with chills and shivering, nausea, vomiting, weight loss and generalized pruritus. INVESTIGATIONS: Physical examination, laboratory evaluation, transabdominal ultrasonography, magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography, brush cytology, laparotomy and histopathology. DIAGNOSIS: Bile duct duplication with coexistence of distal cholangiocarcinoma. MANAGEMENT: En bloc resection (including the duodenum, pancreatic head and adjacent lymph nodes), hepaticojejunostomy and pylorus-saving Whipple operation.

Effect of Helicobacter pylori eradication on insulin resistance, serum lipids and low-grade inflammation.

BACKGROUND/AIM: Many studies have revealed a close relationship between Helicobacter pylori (HP) infection and insulin resistance. The aim of this study was to investigate the effects of HP eradication on insulin resistance, serum lipids and low-grade inflammation. MATERIALS AND METHODS: This was a prospective, open-label, single-center study which consisted of 159 patients. The patients with HP infection received a 14-day sequential regimen. A HOMA-IR (homeostasis model assessment of insulin resistance) level was used to assess insulin resistance. RESULTS: Eighty-eight patients with HP infection and seventy-one patients without HP infection were studied. HOMA-IR, total cholesterol (TC), triglyceride (TG), LDL cholesterol (LDL-C) and C reactive protein (CRP) levels were significantly higher and HDL-cholesterol (HDL-C) levels were significantly lower in patients with HP infection compared to the patients without HP infection (P<0.05). The HP eradication rates with a sequential regimen in dyspeptic patients were 53.4%. Six weeks after the end of eradication therapy, the mean fasting insulin, HOMA-IR, TC, TG, LDL-C, and CRP levels in patients with successful eradication were significantly decreased from the pretreatment levels (P<0.05) and HDL-C level was significantly increased from the pretreatment levels (P<0.05). The mean fasting insulin, HOMA-IR, TC, TG, LDL-C, CRP levels and HDL-C levels in patients with unsuccessful eradication were not significantly changed from pretreatment levels (P<0.05). CONCLUSION: This study showed beneficial effects of HP eradication on insulin resistance, atherogenic lipid abnormalities and low-grade inflammation. The results suggest that HP eradication may prevent coronary artery disease and metabolic syndrome.