Antimicrobial and anti-virulence activities of 4-shogaol from grains of paradise against gram-negative bacteria: Integration of experimental and computational methods.

ETHNOPHARMACOLOGICAL RELEVANCE: Bacterial resistance to antibiotics is a growing global concern, highlighting the urgent need for new antimicrobial candidates. Aframomum melegueta was traditionally used for combating urinary tract and soft tissue infections, which implies its potential as an antimicrobial agent. AIM OF STUDY: This study was designed to explore the antibacterial and anti-virulence capabilities of 4-shogaol isolated from A. melegueta seeds versus gram-negative bacteria: Serratia marcescens, Klebsiella pneumoniae, Acinetobacter baumannii, and the clinically important pathogen Pseudomonas aeruginosa. MATERIALS AND METHODS: 4-Shogeol was isolated from A. melegueta seeds and its MICs were determined for Acinetobacter baumannii (ATCC-17978), Pseudomonas aeruginosa (ATCC-27853), Klebsiella pneumoniae (ATCC-700603), and Serratia marcescens clinical isolate. The anti-efflux activity and effect on the bacterial cell membrane for the compound were evaluated. Furthermore, the anti-virulence activities of the compound were evaluated. The effects of 4-shogeol at sub-MIC on bacterial motility, biofilm formation, and production of virulent enzymes and pigments were assessed. The anti-quorum sensing activities of 4-shogeol were evaluated virtually and by quantification its effect on the expression of quorum sensing encoding genes. The in vivo protection assay was conducted to evaluate the effect of 4-shogaol on the P. aeruginosa capacity to induce pathogenesis in mice. Finally, the effect of shogaol-antibiotics combination was assessed. RESULTS: The research revealed that 4-shogaol's antibacterial action primarily involves disrupting the bacterial cell membrane and efflux pumps. It also exhibited significant anti-virulence effects by reducing biofilm development and repressing virulence factors production, effectively protecting mice against P. aeruginosa infection. Furthermore, when combined with antibiotics, 4-shogaol demonstrated synergistic effects, leading to reduced minimum inhibitory concentrations (MICs) against P. aeruginosa. Its anti-virulence properties were linked to its ability to disrupt bacterial quorum sensing (QS) mechanisms, as evidenced by its interaction with QS receptors and downregulation of QS-related genes. Notably, in silico analysis indicated that 4-shogaol exhibited strong binding affinity to different P. aeruginosa QS targets. CONCLUSION: These findings suggest that 4-shogaol holds promise as an effective anti-virulence agent that can be utilized in combination with antibiotics for treating severe infections caused by gram-positive bacteria.

Cytotoxic and Antioxidant Potential of Launaea mucronata Forssk Essential Oil Growing in Northern Saudi Arabia.

Essential oils are naturally occurring multicomponent combinations of isoprenoids with distinctive odors that are produced by aromatic plants from mevalonic acid. They are extensively applied in aromatherapy for the treatment of various ailments. To investigate the potential therapeutic value of the ingredients in Launaea mucronata essential oil (EO), gas chromatography-mass spectrometry (GC-MS) analysis was used for essential oil characterization. Then, 2,2-diphenyl-1-picrylhydrazyl (DPPH), ß-carotene/linoleic acid, and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays were used to evaluate the antioxidants. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to estimate the cytotoxicity. Following a thorough analysis of the GC-MS chromatogram, 87 components representing 97.98% of the entire EO mixture were identified. N-eicosane (10.92%), 2E,6Z-farnesol (10.74%), and 2Z,6E-farnesyl acetone (46.35%) were determined to be the major components of the oil. When the produced EO was evaluated for its antioxidant properties, it showed a strong inhibitory effect (%) of 65.34 at a concentration of 80 µg/mL. The results (g/mL) showed a positive response against the tested cell lines for HCT-116, MCF-7, and HepG2 (8.45, 10.24, and 6.78 g/mL, respectively). A high-concentration mixture of deadly components consisting of farnesol, bisabolol, eicosane, and farnesyl acetone may be responsible for this significant cytotoxic action, which was especially noticeable in the HepG2 cell line. Molecular docking occurred between farnesol and farnesyl acetone with the target residues of topoisomerases I and II, CDK4/cyclD1, and Aurora B kinases; these showed binding free energies ranging from -4.5 to -7.4 kcal/mol, thus demonstrating their antiproliferative action. In addition, farnesol and farnesyl acetone fulfilled most of the ADME and drug-likeness properties, indicating their activity.

Epidemiological Features of Acute Pancreatitis (AP): Largest Single-Center, Cohort Study in the Western Region of Saudi Arabia.

BACKGROUND: Acute pancreatitis (AP) is a medical emergency which can range in severity from a mild, self-limiting condition to a catastrophic event that results in multiorgan failure. This study aimed to evaluate the epidemiological characteristics of AP. METHODS: This study included all patients diagnosed with AP at King Abdulaziz University Hospital, a tertiary care hospital in Jeddah, Saudi Arabia, between 2017 and 2021. The main aim of this study was to investigate the frequency of AP in patients who present to the hospital with abdominal pain. Secondary objectives included analyzing the causes, complications, severity, and outcomes of the patients. RESULTS: A total of 67 patients were included. AP constituted 11.6% of all cases of patients presenting to the hospital with abdominal pain. Only seven patients presented with severe AP, which was significantly associated with advanced age (over 60 years old). The primary causes of AP were biliary and idiopathic pancreatitis, accounting for 80.6% of the cases. The most frequent complications observed were peripancreatic fluid collection and atelectasis, which occurred in 40.3% of cases. CONCLUSION: AP is a prevalent condition in patients with abdominal pain, with biliary pancreatitis being the leading cause of the disease. The majority of patients exhibited mild to moderate severity of symptoms and experienced positive outcomes when treated appropriately.

A Detached Gallbladder Situated Below the Transverse Colon: A Case Report of an Unusual Position.

This report presents an unforeseen event involving the detachment of the gallbladder without any traumatic cause, which was incidentally detected during a scheduled laparoscopic cholecystectomy procedure. The incidence of total congenital gallbladder detachment from the liver is quite uncommon. The primary difficulty encountered in patients afflicted with this particular medical issue pertains to the intraoperative identification and localization of the gallbladder. The significance of this case report lies in its presentation of a groundbreaking finding that has the potential to provide challenges for surgeons doing laparoscopic cholecystectomy, a commonly performed surgical procedure.

Vitamin K2 (MK-7) Intercepts Keap-1/Nrf-2/HO-1 Pathway and Hinders Inflammatory/Apoptotic Signaling and Liver Aging in Naturally Aging Rat.

Aging is a naturally occurring physiological process with a deleterious impact on various body organs and humans' well-being. The aging population is increasing worldwide, which imposes the need for the exploration of nutritional options that can intercept the impact of the aging processed on various body organs. Vitamin K2 (VK2) is a fat-soluble vitamin with emerging evidence on its therapeutic merits. In the current study, natural aging induced a significant liver deterioration with a disrupted Keap-1/Nrf-2/HO-1 axis and increased COX-2, iNOS and TNF-α expression and apoptotic and fibrotic changes. VK2 administration, on the other hand, improved the biochemical indices of liver function (total protein, albumin, ALT and AST); the suppressed hepatic expression of Keap-1 and increased the hepatic expression of Nrf-2 with a parallel increase in the hepatic activity of HO-1. Subsequently, the liver content and hepatic expression of TNF-α, COX-2 and iNOS were significantly retracted. In context, the liver content and hepatic expression of the fibrotic biomarkers TGFß and TIMP significantly retracted as well. Moreover, the TUNEL assay confirmed the retraction of liver apoptotic changes. Of notice, electron transmission microscope examination confirmed the preservation of mitochondrial functions and preservation of the ultra-microscopical structures. In conclusion, the VK2-mediated interception of aging-induced Keap-1/Nrf-2/HO-1 signaling suppressed the hepatic contents of inflammatory and fibrotic biomarkers, as well as apoptotic changes with preservation of the hepatic architectural and functional status. VK2 can be presumed to be an effective nutritional supplement to the aging population to spare the liver, amongst other body organs, against aging-induced deleterious injury.

Risk of Biliary Events After Selective Cholecystectomy During Biliopancreatic Diversion with Duodenal Switch.

BACKGROUND: Approximately 20 % of adults over 40 years of age in the USA develop cholelithiasis (Topart et al. Surg Obes Relat Dis. 9(4):526-30, 2013). Despite a higher incidence of biliary complications reported in postbariatric patients, it remains controversial whether simultaneous routine cholecystectomy should be performed during biliopancreatic diversion and duodenal switch (BPD/DS) or if a selective approach is more appropriate. The aim of this study was to evaluate incidence of biliary complications in patients who underwent BPD/DS without simultaneous cholecystectomy. METHODS: Retrospective review of all patients who underwent BPD/DS between 2006 and 2012 was performed. RESULTS: A total of 361 consecutive patients were included in the study with mean age of 44.8 years (range 20-72), mean body weight of 317.2 lbs (range 205-547), and average body mass index (BMI) of 50.5 kg/m(2) (range 34-71.4). Ninety-seven patients were males (26.8 %). Out of 239 patients who still had their gallbladder after the BPD/DS, 52 patients (22.7 %) developed subsequent biliary symptoms (13 patients (5.4 %) in the first year, 25 (11 %) in the second year, and 14 (6.1 %) beyond the second year). During the study period, 40 patients eventually underwent elective laparoscopic cholecystectomy, and 11 had urgent cholecystectomy (9 laparoscopic and 2 open). One patient underwent open common bile duct exploration for ascending cholangitis. Average follow-up was 31 months (12-72 months) with follow-up rate of 95.6 % at 12 months and 92.8 % at 18 months. CONCLUSIONS: Leaving normal gallbladder in situ after BPD/DS is associated with an acceptable risk of biliary events. Risk of developing common bile duct stones is low; however, it may create treatment challenges.

Does preoperative diabetes mellitus affect weight loss outcome after biliopancreatic diversion with duodenal switch?

BACKGROUND: Preoperative type 2 diabetes mellitus (T2 DM) has previously been reported as an independent predictor for suboptimal (≤40%) weight loss after Roux-en-Y gastric bypass in patients with T2 DM compared with patients who do not have T2 DM. This association has not been shown to apply to patients who undergo biliopancreatic diversion with duodenal switch (BPD/DS). BPD/DS is currently the most effective bariatric operation to treat T2 DM. OBJECTIVES: We designed a study to determine if the reported suboptimal weight loss seen in patients with T2 DM undergoing Roux-en-Y gastric bypass is also seen in those undergoing BDP/DS. SETTING: Independent, university-affiliated teaching hospital. MATERIALS AND METHODS: Retrospective chart review of a prospectively maintained database was performed on data on 152 patients who underwent robotically assisted laparoscopic BPD/DS from 2008 to 2012. Patients were divided into 2 groups: those with a preoperative diagnosis of T2 DM (Group 1, n = 51) versus those without a preoperative diagnosis of T2 DM (Group 2, n = 101). Perioperative complications and postoperative weight loss between the 2 groups were compared. RESULTS: At 1 month postoperatively, Group 1 had a higher percentage of excess weight loss (%EWL) of 20.9% compared with Group 2 of 17.9% (P<.05). At 3, 6, 9, 12, and 18 months postoperatively, both groups had statistically comparable %EWL (P>.05). Thirty-day perioperative complications were higher in Group 1 compared with those in Group 2 (7.8% and 3.9%, respectively). Reoperation rates were similar in both groups (1.9%). No mortality was recorded in this series. CONCLUSION: Patients with diabetes had a similar weight loss outcome after BPD/DS compared with those who did not have diabetes.

Short- and long-term outcomes following percutaneous cholecystostomy for acute cholecystitis in high-risk patients.

BACKGROUND: Percutaneous cholecystostomy is a less invasive method to treat acute cholecystitis in patients who are critically ill or have serious medical comorbidities precluding the use of general anesthesia. It remains controversial whether interval cholecystectomy is warranted. The objectives of the study were to determine the success rate and complications of percutaneous cholecystostomy and the proportion of patients without recurrent attacks in whom interval cholecystectomy was not needed. METHODS: This was a retrospective review to determine the outcomes after percutaneous cholecystostomy for acute calculous cholecystitis between 1995 and 2007. Administrative data were used to better capture recurrent symptoms requiring treatment. RESULTS: Sixty-eight patients with a mean age of 74 years were identified. Sixty-seven (98.5%) underwent successful insertion of the cholecystostomy tubes. Eleven patients suffered tube-related complications, including tube dislodgment (9), tube blockage (1), and bleeding that was controlled with conservative management (1). The initial episode of cholecystitis was treated successfully in 58 patients (85%). The overall in-hospital and 30-day mortality were both 15% (10 patients). A total of 7 patients (10%) underwent cholecystectomy while still in hospital. There were 39 patients at risk for recurrent disease who survived the initial episode and did not receive an interval cholecystectomy. Of these 39 patients, 16 (41%) suffered recurrent gallbladder-related disease. CONCLUSIONS: Percutaneous cholecystostomy is an alternative to cholecystectomy in patients with acute calculous cholecystitis who are at high risk for surgical mortality and morbidity. It appears to have a low complication rate and good clinical success. Because a significant number of patients suffer recurrent attacks, elective cholecystectomy should be considered routinely. Unfortunately, firm criteria for selecting percutaneous cholecystostomy over cholecystectomy are lacking, and the surgeon's clinical judgment is critically important.