Dietary menhaden fish oil supplementation suppresses lipopolysaccharide-induced neuroinflammation and cognitive impairment in diabetic rats.

CONTEXT: Menhaden fish oil (FO) is widely recognized for inhibiting neuroinflammatory responses and preserving brain function. Nevertheless, the mechanisms of FO influencing brain cognitive function in diabetic states remain unclear. OBJECTIVE: This study examines the potential role of FO in suppressing LPS-induced neuroinflammation and cognitive impairment in diabetic animals (DA). MATERIALS AND METHODS: Thirty male Wistar rats were divided into 5 groups: i) DA received LPS induction (DA-LPS); ii) DA received LPS induction and 1 g/kg FO (DA-LPS-1FO); iii) DA received LPS induction and 3 g/kg FO (DA-LPS-3FO); iv) animals received normal saline and 3 g/kg FO (NS-3FO) and v) control animals received normal saline (CTRL). Y-maze test was used to measure cognitive performance, while brain samples were collected for inflammatory markers and morphological analysis. RESULTS: DA received LPS induction, and 1 or 3 g/kg FO significantly inhibited hyperglycaemia and brain inflammation, as evidenced by lowered levels of pro-inflammatory mediators. Additionally, both DA-LPS-1FO and DA-LPS-3FO groups exhibited a notable reduction in neuronal damage and glial cell migration compared to the other groups. These results were correlated with the increasing number of entries and time spent in the novel arm of the Y-maze test. DISCUSSION AND CONCLUSION: This study indicates that supplementation of menhaden FO inhibits the LPS signaling pathway and protects against neuroinflammation, consequently maintaining cognitive performance in diabetic animals. Thus, the current study suggested that fish oil may be effective as a supporting therapy option for diabetes to avoid diabetes-cognitive impairment.

Hematological, biochemical, and histopathological evaluation of the Morus alba L. leaf extract from Brunei Darussalam: Acute toxicity study in ICR mice.

Background: Studies have reported that the phytochemical content of Mulberry (Morus alba Linn.) is influenced by the area where it grows. On the other hand, the study of the bioactivity and toxicity of mulberry leaves from Brunei Darussalam still needs to be completed. In particular, the investigation regarding the safe dose for Mulberry's application from Brunei Darussalam has yet to be studied. Hence, toxicity information must be considered even though the community has used it for generations. Aim: This study investigated Morus alba ethanolic leaf extract (MAE) to observe the acute toxicity in mice. Methods: In particular, this study utilized 12 female Institute of Cancer Research mice, 8 weeks old, divided into 2 groups: the control group and the MAE group (2,000 mg/kg single dose). Physiology, hematology, biochemistry, and histology were analyzed during the study. Results: The examination result indicated no mortality and behavioral changes throughout the testing period. However, the mice developed mild anemia and leukopenia, followed by decreased numbers of neutrophils, lymphocytes, and monocytes. In addition, the mice developed a mild hepatocellular injury, indicated by significant (p < 0.05) elevations of both alanine aminotransferase (ALT) and aspartate transaminase (AST). The histopathological findings of the liver were also consistent with the increment of ALT and AST, indicating mild hepatocellular necrosis through the eosinophilic cytoplasm and pyknosis (p > 0.05). Conclusion: It was evident that a single oral administration of MAE was not lethal for mice (LD50, which was higher than 2,000 mg/kg). However, the administration of high doses of MAE must be carefully considered.

Bioactivity, phytochemistry studies and subacute in vivo toxicity of ethanolic leaf extract of white mulberry (Morus alba linn.) in female mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional uses of Morus alba L. leaf extracts (MLE) have been reported for treating hyperglycaemia and diabetes. Phytochemical compounds in the leaves demonstrated the ability to enhance insulin sensitivity and ß-cell secretory function, suggesting their potential value in reducing blood glucose and treating diabetes. However, the phytochemical constituents and safety of the herbal medicines need to be verified in each experimental field from different growing areas. Studies on the phytochemistry and toxicity of Morus alba leaves in Southeast Asia, especially in Brunei, have never been investigated. AIM OF THE STUDY: This study aimed to investigate the bioactivity and phytochemistry of Morus alba ethanolic leaf extract from Brunei Darussalam and its subacute toxic effects in the Institute of Cancer Research (ICR) female mice. MATERIALS AND METHODS: The phenolic yield and antioxidant of the extract were analysed. Meanwhile, liquid chromatography-mass spectrometry and high-performance liquid chromatography were utilised to determine the phenolic compound of the MLE. In the subacute toxicity study, twenty-five female mice were randomly divided into five groups: the control group, which received oral gavage of 5% dimethyl sulfoxide solvent (DMSO), and the MLE treatment group, which received the extract at a dose of 125, 250, 500 and 1000 mg/kg. Physiology, haematology, biochemistry, and histology were evaluated during the study. RESULTS: Morus alba leaf depicted total phenolic 10.93 mg gallic acid equivalents (GAE)/g dry weight (DW), flavonoid 256.67 mg quercetin equivalents (QE)/g DW, and antioxidant bioactivity content of 602.03 IC50 µg/mL and 13.21 mg Fe2+/g DW. Twenty compounds in the Morus alba ethanolic leaf extract were identified, with chlorogenic acid (305.60 mg/100 g DW) as the primary compound. As for subacute toxicity in this study, neither mortality nor haematological changes were observed. On the other hand, administration of 500 and 1000 mg/kg MLE resulted in mild hepatocellular injury, as indicated by a significant (p < 0.05) increase in liver enzyme activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The histopathological score showed mild hepatocellular necrosis in administering 250, 500, and 1000 mg/kg of MLE. The parameters of renal injury were within normal limits, with the increase in eosinophilic cytoplasm observed in the histological scoring at 1000 mg/kg of MLE. CONCLUSIONS: Morus alba leaf extract showed abundant polyphenols. In a study on subacute toxicity, MLE caused mild hepatotoxicity in mice. The toxic effect of the extract may be due to kaempferol and chlorogenic acid compounds. The 125 mg/kg MLE dose was safe with no adverse effects.

Protective potential of fish oil supplementation against insulin resistance and pancreatic islet damage in STZ-induced Wistar rats.

Background: Fish oil, which is regarded as the primary source of omega-3 fatty acids, has been long studied for its potential as an antidiabetic therapy. However, its protective ability against insulin resistance and pancreatic islet alteration remains unclear and controversial. Aim: To investigate the beneficial effects of fish oil consumption on the progression of insulin resistance and pancreatic islet dysfunction in a rat model of diabetes. Methods: Diabetic rats model (n = 30) were divided into five groups and received; 1) NS injection + NS oral (normal control); 2) NS injection + 3 g/kg fish oil (fish oil control); 3) streptozotocin (STZ) injection + NS oral [diabetes control (DC)]; 4) STZ injection + 1 g/kg fish oil (DFO1); and 5) STZ injection + 3 g/kg fish oil (DFO3). Fasting blood insulin was analyzed by commercial rat insulin enzyme-linked immunosorbent assay; meanwhile, the determination of insulin sensitivity was calculated by homeostatic model assessment of insulin resistance (HOMA-IR) and homeostatic model assessment of beta-cell function. A histological study was conducted on pancreas tissue using H and E staining. Results: Fish oil supplementation reduced hyperglycemia and ameliorated HOMA-IR in STZ-induced animal models indicating that fish oil supplementation improved insulin sensitivity. Furthermore, animals treated with fish oil at a dose of 3 g/kg (DFO3) showed an enhancement in pancreatic islets, which was displayed by less abnormal structures than DC animals. This could imply that the administration of fish oil, especially rich in bioactive omega-3 fatty acids effectively inhibits insulin resistance and restore islet of Langerhans alteration in rats injected with STZ. Conclusion: Thus, the current study suggested that fish oil supplementation could support the treatment of diabetes but should not be considered as an alternative therapy.

The value of fecal tumor M2 pyruvate kinase as a diagnostic tool for colorectal cancer screening.

AIM: to evaluate the performance of fecal tumor M2 pyruvate kinase (M2PK) as a diagnostic biomarker for colorectal cancer (CRC) screening in high-risk or symptomatic populations. METHODS: consecutive patients (N=328) who were referred for elective colonoscopy were prospectively enrolled. One walnut-sized stool sample was collected from each patient for analysis of tumor M2PK content using an ELISA kit. No dietary restrictions were applied. The clinical pathologists who conducted the M2PK analyses were blinded to the patients' confirmed diagnoses. Levels of fecal tumor M2PK were compared with histopathological results from colorectal biopsies. RESULTS: of the 328 patients who underwent colonoscopy examinations, 197 (60.1%) were men and 131 (39.9%) were women. Based on histopathological examination, 83 (25.3%) patients had normal bowel histology, 42 (12.8%) patients had CRC, 67 (20.4%) patients had adenoma, 19 (5.8%) patients had inflammatory bowel disease, three (0.9%) patients had amoebic colitis, and 114 (34.8%) patients had infective colitis. The cutoff level for tumor M2PK concentration was defined as 4.00 U/mL. The sensitivity, specificity, positive predictive value, and negative predictive value of the M2PK test were 71.4%, 71.0%, 73.5%, and 94.4%, respectively. There was a significant association between CRC and fecal tumor M2PK level (P<0.001). The M2PK test detected 16 tumors among 67 (23.9%) cases of adenoma, eight tumors among 19 (42.1%) cases of inflammatory bowel disease, 35 tumors among 114 (30.7%) cases of infective colitis, and two tumors among three (66.7%) cases of amoebic colitis. CONCLUSION: the fecal tumor M2PK test has good sensitivity and specificity for CRC detection, especially in high-risk or symptomatic populations.

The effectiveness of endoscopic retrograde cholangiopancreatography in the management of patients with jaundice at Cipto Mangunkusumo Hospital, Jakarta.

AIM: to evaluate endoscopic retrograde cholangiopancreatography (ERCP) benefits in treating patients with clinical appearance of yellowish discoloration. METHODS: a descriptive retrospective cross-sectional study was performed on 122 patients at Cipto Mangunkusumo Hospital from January 2008 to December 2010. The main complained was yellowish discoloration of the skin. ERCPs were performed as appropriate, and then the distribution of disease entity, results of procedure and complications were noted. RESULTS: subjects of this study consist of 63 males (52%) and 59 females (48%), 7 patients have undergone ERCP 2 times. Data showed 63 cases (51%) were indicated by stone and 52 cases (43%) by tumor/mass and 7 cases by infection (6%). Ten out of 122 cases (7%) showed normal results. Difficult canulation was encountered in 23 cases (18%) as access to the CBD could not be obtained. From 53 cases with stone, the extraction was successful in 43 (81%) including while 12 procedures with high grade of difficult ERCP left stone remnants (23%), and the remaining 10 procedures entailed stones retention (19%). Radioopaque stones found in 2 cases (4%) and radioluscent in 51 cases (96%). Stent placement was done in CBD (30 cases, 83%), pancreatic duct (4 cases, 11%), and extraneous CBD (2 cases, 5%). Complications found 3 cases (2%) migration stent outside CBD in 2 cases, 1 case with crand radioluscentin 51 acked basket. CONCLUSION: ERCP procedure is really helpful in assisting clinicians to diagnose and manage therapeutic measures, especially in pancreaticobilliar tract disorder, while performing stone extraction and stent placement.

Molecular profile of colorectal cancer in Indonesia: is there another pathway?

Colorectal cancer is an emerging public health problem in Indonesia and currently ranks among the three highest cancers. Lack of a colonoscopy screening and lifestyle changes might contribute to it. In the last few decades, there is an increasing interest towards the contribution of genetic-environment interaction in colorectal carcinogenesis. Some studies have indicated that CRC might develop through several different pathways; the three major routes are chromosomal instability (CIN), microsatellite instability (MSI), and inflammatory pathways. An earlier study on clinical epidemiology of CRC in Indonesia showed that the majority of patients were diagnosed between 45 and 50 years old, with a mean age around 47 years old. Further studies showed that most young Indonesian cases of CRC do not have hereditary characteristics; however, the CRC did not follow the conventional pathways of sporadic CRC (the CIN) pathway. Rather, it is a mixed of MSI and inflammatory pathways. Immunohistochemical studies showed that the proportion of patients with negative mismatch repair proteins was 43.5% for MSH2 and 83.5% for MLH1. Along the sporadic colorectal carcinogenesis pathway, there was a specific role of cyclooxygenase-2 (COX-2) enzyme during the polyp formation. COX-2 expression was reported in about 80% CRC cases worldwide. However, our study found only 49% of COX-2 expression among the CRC patients. Interestingly, an inflammatory marker, the nucleus factor κB (NF-κB), was expressed in about 73.5% cases, in line with a previous study. More recently, KRAS has been used as a potential tumor marker to select treatment and its expression was reported to be as high as 30%-40% worldwide. However, we found that KRAS gene expression was only 16.3%. Our findings support that CRC patients in Indonesian might follow a distinct pathway, a hypothesis that deserves further exploration.