Berberine Attenuates Cerulein-Induced Acute Pancreatitis by Modulating Nrf2/NOX2 Signaling Pathway via AMPK Activation.

AMP-activated protein kinase (AMPK) is the master regulator of cellular energy which gets activated during energy stress and restores tissue homeostasis. AMPK is widely expressed in the pancreas and is involved in protein synthesis. In cerulein-induced acute pancreatitis (AP), diminished AMPK activity in the pancreatic tissue may be associated with pancreatic inflammation and oxidative stress.

Combined KRAS-MAPK pathway inhibitors and HER2-directed drug conjugate is efficacious in pancreatic cancer.

Targeting the mitogen-activated protein kinase (MAPK) cascade in pancreatic ductal adenocarcinoma (PDAC) remains clinically unsuccessful. We aim to develop a MAPK inhibitor-based therapeutic combination with strong preclinical efficacy. Utilizing a reverse-phase protein array, we observe rapid phospho-activation of human epidermal growth factor receptor 2 (HER2) in PDAC cells upon pharmacological MAPK inhibition.

A Pilot Study of Paricalcitol plus Nanoliposomal Irinotecan and 5-FU/LV in Advanced Pancreatic Cancer Patients after Progression on Gemcitabine-Based Therapy.

Purpose: Vitamin D analogues remodel the desmoplastic stroma, and improve vascularity and efficacy of chemotherapy in preclinical pancreas cancer models.

Patients And Methods: We conducted a pilot study to evaluate the safety and preliminary efficacy of the vitamin D analogue paricalcitol in combination with nanoliposomal irinotecan (Nal-iri) plus 5-fluorouracil/leucovorin (5-FU/LV) in patients with advanced pancreatic cancer who had progressed on gemcitabine-based therapy. Two dose levels (DL) of paricalcitol were tested: fixed dose weekly (75 mcg, DL1) and weight-based weekly (7 mcg/kg, /DL2).

Exploration of cytotoxic potential and tubulin polymerization inhibition activity of -stilbene-1,2,3-triazole congeners.

To scrutinize -stilbene based molecules with potential anticancer and tubulin polymerization inhibition activity, a new series of -stilbene-1,2,3-triazole congeners was designed and synthesized a click chemistry protocol. The cytotoxicity of these compounds 9a-j and 10a-j was screened against lung, breast, skin and colorectal cancer cell lines. Based on the results of MTT assay, we further evaluated the selectivity index of the most active compound 9j (IC 3.

Acetaminophen induced hepatotoxicity: An overview of the promising protective effects of natural products and herbal formulations.

Background: The liver plays an important role in regulating the metabolic processes and is the most frequently targeted organ by toxic chemicals. Acetaminophen (APAP) is a well-known anti-allergic, anti-pyretic, non-steroidal anti-inflammatory drug (NSAID), which upon overdose leads to hepatotoxicity, the major adverse event of this over-the-counter drug.

Purpose: APAP overdose induced acute liver injury is the second most common cause that often requires liver transplantation worldwide, for which N-acetyl cysteine is the only synthetic drug clinically approved as an antidote.

COVID-19 and fibrosis: Mechanisms, clinical relevance, and future perspectives.

Coronavirus 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has had significant impacts worldwide since its emergence in December, 2019. Despite a high recovery rate, there is a growing concern over its residual, long-term effects. However, because of a lack of long-term data, we are still far from establishing a consensus on post-COVID-19 complications.

Oncogenic -Induced Feedback Inflammatory Signaling in Pancreatic Cancer: An Overview and New Therapeutic Opportunities.

Pancreatic ductal adenocarcinoma (PDAC) remains highly refractory to treatment. While the oncogene is present in almost all PDAC cases and accounts for many of the malignant feats of PDAC, targeting KRAS or its canonical, direct effector cascades remains unsuccessful in patients. The recalcitrant nature of PDAC is also heavily influenced by its highly fibro-inflammatory tumor microenvironment (TME), which comprises an acellular extracellular matrix and various types of non-neoplastic cells including fibroblasts, immune cells, and adipocytes, underscoring the critical need to delineate the bidirectional signaling interplay between PDAC cells and the TME in order to develop novel therapeutic strategies.

Design, synthesis, and biological evaluation of N-(4-substituted)-3-phenylisoxazolo[5,4-d]pyrimidin-4-amine derivatives as apoptosis-inducing cytotoxic agents.

A library of new 3-phenylisoxazolo[5,4-d]pyrimidines (8-10) was designed based on a scaffold hybridization technique incorporating the important pharmacophoric features of 4-aminopyrimidine and phenyl isoxazole scaffold which is renowned for its BET inhibition activity. The designed molecules were synthesized and evaluated with the NCI-60 cell line panel. Examination by NCI-60 cell lines at single-dose and the five-dose study showed that compound 10h exhibited promising growth inhibitory effects with GI values on various cancer cell lines such as HCT-15 (Colon Cancer)-0.

Inhibition of discoidin domain receptors by imatinib prevented pancreatic fibrosis demonstrated in experimental chronic pancreatitis model.

Discoidin domain receptors (DDR1 and DDR2) are the collagen receptors of the family tyrosine kinases, which play significant role in the diseases like inflammation, fibrosis and cancer. Chronic pancreatitis (CP) is a fibro-inflammatory disease in which recurrent pancreatic inflammation leads to pancreatic fibrosis. In the present study, we have investigated the role of DDR1 and DDR2 in CP.

Molecular updates on berberine in liver diseases: Bench to bedside.

Liver diseases are life-threatening illnesses and are the major cause of mortality and morbidity worldwide. These may include liver fibrosis, liver cirrhosis, and drug-induced liver toxicity. Liver diseases have a wide prevalence globally and the fifth most common cause of death among all gastrointestinal disorders.

Nimbolide ameliorates pancreatic inflammation and apoptosis by modulating NF-κB/SIRT1 and apoptosis signaling in acute pancreatitis model.

Acute pancreatitis (AP) is a potential gastrointestinal problem most commonly associated with pancreatic inflammation and acinar cells injury. Nimbolide (NB), isolated from the tree Azadirachta indica, possesses antioxidant and anti-inflammatory effects. Here, we aimed to investigate the pancreatic protective effects of NB in ameliorating cerulein-induced pancreatic inflammation and apoptosis in AP model and evaluate the potential mechanism of action.

Borneol protects against cerulein-induced oxidative stress and inflammation in acute pancreatitis mice model.

Borneol is a commonly used flavouring substance in traditional Chinese medicine, which possesses several pharmacological activities including analgesic, antiinflammatory, and antioxidant properties. The aim of this study was to investigate the effects of borneol on cerulein-induced acute pancreatitis (AP) model. Swiss albino mice were pretreated with borneol (100 and 300 mg/kg) daily for 7 days, before six consecutive injections of cerulein (50 μg/kg/hr, intraperitoneally).

Piperlongumine attenuates bile duct ligation-induced liver fibrosis in mice via inhibition of TGF-β1/Smad and EMT pathways.

Liver fibrosis (LF) is a progressive liver injury that may result in excessive accumulation of extracellular matrix (ECM). However, transforming growth factor-beta (TGF-β) and epithelial to mesenchymal transition (EMT) play a central role in the progression of LF through the activation of matrix producing hepatic stellate cells (HSCs). Piperlongumine (PL), an alkaloid extracted from Piper longum, has been reported to possess anti-inflammatory and antioxidant activities in various diseases but its hepatoprotective and antifibrotic effects have not been reported yet.

Berberine attenuates severity of chronic pancreatitis and fibrosis via AMPK-mediated inhibition of TGF-β1/Smad signaling and M2 polarization.

Berberine (BR) acts as an AMP-activated protein kinase (AMPK) activator which possesses antioxidant and anti-inflammatory properties. In this study, we have investigated the effects of BR against cerulein-induced chronic pancreatitis (CP) via inhibition of TGF-β/Smad signaling and M2 macrophages polarization in AMPK dependent manner. Cerulein-induced CP mice were treated with BR (3 and 10 mg/kg), intraperitoneally every day for 21 days.

Nimbolide abrogates cerulein-induced chronic pancreatitis by modulating β-catenin/Smad in a sirtuin-dependent way.

Chronic pancreatitis (CP) is one of the leading causes of mortality worldwide with no clinically approved therapeutic interventions. The present study was designed to investigate the protective effect of nimbolide (NB), an active constituent of neem tree (Azadirachta indica), by targeting β-catenin/Smad/SIRT1 in cerulein-induced CP model. The effects of NB was investigated on cerulein (50 μg/kg/hr*6 exposures /day, 3 days a week for 3 weeks) induced CP in mice.

Crocin, an active constituent of Crocus sativus ameliorates cerulein induced pancreatic inflammation and oxidative stress.

Acute pancreatitis (AP) is a disorder of the pancreas marked by profound inflammation and oxidative stress. Phytoconstituents presents an important toolbox of preventive strategies to combat inflammatory disorders. To this end, we selected the active constituent of Crocus sativus, crocin for evaluation against cerulein-induced AP, owing to its promising antiinflammatory activity in acute as well as chronic inflammatory conditions.

Cerulein-induced chronic pancreatitis in Swiss albino mice: An improved short-term model for pharmacological screening.

There is a need for short-term, reliable and reproducible animal model of chronic pancreatitis (CP) in small animals like mice. This study was aimed to establish the 9 exposures of cerulein-induced CP in mice. Repeated intraperitoneal cerulein injections were performed at 6 consecutive doses (50 μg/kg)/day, 3 days a week for 3 weeks to induce chronic pancreatitis in Swiss albino mice.