Pancreatic ductal adenocarcinoma (PDAC) is most often detected at an advanced stage due to a lack of symptoms at the first stage. PDAC is relatively uncommon, and screening of the asymptomatic population is not feasible or cost-effective. Therefore, screening of individuals in high-risk groups is recommended. Diabetes mellitus (DM) is associated with PDAC, and patients with DM are recognized as a high-risk group for PDAC. Here, we review the complex relationship between pancreatic cancer and DM, including the role of diabetes as a risk factor for pancreatic cancer and its role in inducing the destruction of islet β cells and insulin resistance. We also review the current study about discriminating DM with pancreatic cancer from normal DM and the model for early screening of pancreatic cancer in DM.

Myrica nagi Thunb., belonging to the family Myricaceae, is used in Indian traditional medicine to treat diarrhea. This study aimed to assess the anti-diarrheal activity of the aqueous extract of stem bark of Myrica nagi (AEMN) using castor oil-induced diarrhea and charcoal meal tests in albino rats.

Wistar rats of either sex were divided into five groups (n = 6). In castor oil-induced diarrhea, castor oil (10 mL/kg p.o.) was used as an inducer, and loperamide (3 mg/kg p.o.) was used as the standard drug. However, in charcoal-induced diarrhea, atropine sulphate (5 mg/kg p.o.) was used as a standard drug. AEMN was administered to rats at 125, 250, and 500 mg/kg p.o., respectively. These rats were monitored for 4 h and the first defecation time was noted. The fecal matter was collected every 30 min and its frequency and weight were measured. Charcoal meal test was performed on the rats.

AEMN in different doses significantly reduced the first fecal output, the cumulative number of feces, and the cumulative weight of feces after four hours in the castor oil-induced diarrheal model compared with the control group. The extract at 250 mg/kg p.o. and 500 mg/kg also significantly (p < 0.001) reduced the distance travelled by the charcoal.

AMEN alleviates diarrhea and related problems at higher dose i.e. 500 mg/kg. Tannins, flavonoids and terpenoids may be responsible for the antidiarrheal effects.

The world has witnessed increased incidences of severe acute hepatitis in children since early 2021, in which the total number of global cases was over 1,000 in July 2022. Those cases of severe acute hepatitis were intriguing, as they were not caused by the common hepatitis A-E viruses. Additionally, the cause remains unknown to date, thus named as severe acute hepatitis of unknown etiology. The World Health Organization, supported by regional and national health agencies, has issued the working case definitions in order to closely monitor the development of this disease worldwide. As one of its member states, Indonesia has also adopted the case definitions and subsequently issued a health decree to increase public awareness and to conduct an early surveillance on this illness. It remains to be seen whether this updated public health policy would be successful to control the numbers of cases of severe acute hepatitis of unknown etiology in Indonesia.

Immunocompromised status and interrupted routine care may render patients with cirrhosis vulnerable to the coronavirus disease 2019 (COVID-19) pandemic. A nationwide dataset that includes more than 99% of the decedents in the U.S. between April 2012 and September 2021 was used. Projected age-standardized mortality during the pandemic were estimated according to prepandemic mortality rates, stratified by season. Excess deaths were determined by estimating the difference between observed and projected mortality rates. A temporal trend analysis of observed mortality rates was also performed in 0.83 million decedents with cirrhosis between April 2012 and September 2021 was included. Following an increasing trend of cirrhosis-related mortality before the pandemic, with a semiannual percentage change (SAPC) of 0.54% [95% confidence interval (CI): (0.0–1.0%), p=0.036], a precipitous increase with seasonal variation occurred during the pandemic (SAPC 5.35, 95% CI: 1.9–8.9, p=0.005). Significantly increased mortality rates were observed in those with alcohol-associated liver disease (ALD), with a SAPC of 8.44 (95% CI: 4.3–12.8, p=0.001) during the pandemic. All-cause mortality of nonalcoholic fatty liver disease rose steadily across the entire study period with a SAPC of 6.79 (95% CI: 6.3–7.3, p<0.001). The decreasing trend of HCV-related mortality was reversed during the pandemic, while there was no significant change in HBV-related deaths. While there was significant increase in COVID-19-related deaths, more than 55% of the excess deaths were the indirect impact of the pandemic. We observed an alarming increase in cirrhosis-related deaths during the pandemic especially for ALD, with evidence in both direct and indirect impact. Our findings have implications on formulating policies for patients with cirrhosis.

Increasing confidence in using in vitro and in silico model-based data to aid the chemical risk assessment process is one of the most significant challenges faced by regulatory authorities. A crucial concern is taking full advantage of scientifically valid physiologically-based kinetic (PBK) models. The present study aims to present a very innovative solution of a fully generic PBK model written as a set of ordinary differential equations (ODE).

This study proposes an innovative and unified modeling framework for writing PBK equations as matrix ODE and their solutions, expressed with matrix products. This generic PBK solution considers as many state variables as needed to quantify chemical absorption, distribution, metabolism, and excretion processes within living organisms when exposed to chemical substances.

We first introduce our PBK modeling framework, with all the intermediate steps from the matrix ODE to the exact solution. Then we apply this framework to bioaccumulation testing before illustrating its concrete use through complementary case studies regarding species, compounds, and model complexity.

This generic PBK model makes it possible for any compartmentalization to be considered, as well as all appropriate interconnections between compartments and with the external medium.

Traumatic brain injuries (TBI), ischemic stroke, hemorrhagic stroke, brain tumors, and seizures have diverse and sometimes overlapping associated breathing patterns. Homeostatic mechanisms for respiratory control are intertwined with complex neurocircuitry, both centrally and peripherally. This paper summarizes the neurorespiratory control and pathophysiology of its disruption. It also reviews the clinical presentation, ventilatory management, and emerging therapeutics. This review additionally serves to update all recent preclinical and clinical research regarding the spectrum of respiratory dysfunction. Having a solid pathophysiological foundation of disruptive mechanisms would permit further therapeutic development. This novel review bridges experimental/physiological data with bedside management, thus allowing neurosurgeons and intensivists alike to rapidly diagnose and treat respiratory sequelae of acute brain injury.

The liver contributes substantially to the metabolic transformation and transport of lipids and lipoproteins. These bioactive substances represent a heterogeneous group of molecules with pivotal roles in diverse pathological processes as well as disease progression, the advent of complications, and the response to specific treatments in the context of cirrhosis. The present mini-review aims to summarize the underlying mechanisms regarding lipid changes across divergent circumstances. Recent evidence suggests the prognostic value of lipids/lipoproteins and their close relationship to an increased risk mortality among cirrhotic patients. However, more research regarding the development of risk stratification and therapeutic strategies based on altered lipid profiles in patients with cirrhosis is warranted.

The pathomorphological features of primary biliary cholangitis (PBC) is well-established. However, the distinction between PBC recurrence, and T cell-mediated rejection or chronic rejection remains as a challenge for pathologists. Due to the overlapping morphology, correct diagnosis requires a highly specific discrimination. Accurate diagnosis plays an essential role in patient management since different therapeutic strategies are used. This review focused on the role of pathologists in evaluating the allograft liver biopsy of patients with PBC as the leading cause of native liver cirrhosis. Furthermore, the clinicopathologic features of recurrent PBC, and T cell-mediated rejection or chronic rejection were discussed in detail, with emphasis in distinguishing the histopathology, morphologic variant, and diagnostic pitfalls.

Recently, an anti-trophoblast surface antigen-2 (Trop-2) antibody-drug conjugate targeting Trop-2 positive cancer cells has been approved for treating patients with unresectable locally advanced or metastatic triple-negative breast cancer, who have failed two or more lines of systemic chemotherapy. This has renewed the interest in translational research of Trop-2 positive breast cancer, the gene TACSTD2 and microRNAs that interact with it, and the signaling networks sparked by Trop-2 mediated signaling. In addition, this opinion paper argues that exosomes, extracellular vesicles that are released from Trop-2 positive cancer cells, could play a significant role in cancer progression. Furthermore, diagnostic applications using Trop-2-released exosomes, the cargo exosomes carry, which could be any genetic information such as specific miRNAs, adhesion molecules such as integrins, and metabolites, are yet to be explored in breast cancer patients. Most of the evidence and data are obtained from studies in epithelial cancers other than breast cancers, which have been introduced in the current paper. Therefore, this article briefly summarizes previously published data on other cancer types, forms some hypotheses, and proposes research questions and directions that may be explored further.

In the past decade, with the rapid development of molecular medicine and the application of more sophisticated methods for disease diagnosis and treatment, a number of molecular markers have become available for liver diseases. Pathogenesis-related markers are likely to be effectively discovered and rigorously validated, due to the unique biological links to diseases. The present study reviews the predominant clinical and research articles in the previous decade to provide a pathogenic perspective of current and emerging biomarkers for liver diseases, including hepatocellular neoplasms (e.g. hepatocellular carcinoma), non-neoplastic hepatocellular diseases, intrahepatic biliary diseases, and other liver diseases. Although it remains challenging to cover all markers for the diagnosis and prognosis of liver diseases, current and emerging molecular markers in clinical practice and under investigation are reviewed in a wide spectrum of liver diseases, in order to help clinicians and researchers identify liver disease markers for reference.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is an important inflammation-related biomarker. The present study aimed to determine whether this affects the short-term prognosis of patients with acute-chronic liver failure (ACLF).

The serum sTREM-1 levels of 30 healthy subjects (HS), 40 chronic hepatitis patients without cirrhosis and liver failure (CH), 38 liver cirrhosis (LC) patients, and 59 ACLF patients were evaluated by enzyme-linked immunosorbent assay. The predictive accuracy of the logistic model for survival rate within 90 days in patients with ACLF was determined using the area under the receiver operating characteristic curve (AUC).Kaplan-Meier analysis and log-rank test were performed to revalidate the factors l for the 90-day survival rate of patients with ACLF.

Compared to the CH, LC and HS groups, the serum sTREM-1 levels of ACLF patients were significantly elevated (p < 0.001). In ACLF patients, the serum sTREM-1 levels further increased in non-survivors (661.51 [494.36–1,028.82] pg/mL), when compared to the survivors (440.92 [308.00–523.21] pg/mL) (p = 0.002). The multivariate logistic regression analysis indicated that serum sTREM-1, sodium, and the international normalized ratio (INR) were independent predictors for the 90-day mortality of patients with ACLF. The AUC value for logit (p) in predicting the 90-day prognosis of ACLF patients was 0.89 (0.78–1.00), with a sensitivity of 70%, a specificity of 89.74%.

Serum sTREM-1 is a valuable independent factor for determining the 90-day mortality of ACLF patients. Combining the INR and sodium in the logistic regression model may improve the accuracy in predicting the prognosis.

Although immune checkpoint inhibitors (ICIs) have been a revolutionary milestone in immuno-oncology, immune-related adverse events (irAEs) may occur due to enhanced T cell activation and immune dysregulation. The irAEs can occur as early as within days to reportedly as late as up to 26 weeks. They may affect any organ system in the body, most commonly the luminal gastrointestinal tract, liver, skin, endocrine system, and lungs. The mechanisms of irAEs are complex and have not been fully understood. A breach of self-tolerance, which leads to autoantigen reactivity due to the enhanced activation and infiltration of T cells or the production of autoantibodies, and a non-specific autoinflammatory mechanism have been proposed. Limited data is available on the clinical and pathologic features of ICI-induced liver injury. This review presents an overview of the clinical and common histopathologic features and patterns of ICI-induced liver injury, the differential diagnoses, and the clinical management. Available data suggest that the histopathologic findings of ICI-induced hepatic injury are often non-specific and overlap with other challenging differential diagnoses. Therefore, a good knowledge of the histopathologic spectrum of ICI-induced hepatic injury and their differential diagnoses combined with the serological test results, clinical correlation, and communication with the clinical team is necessary to make an accurate and timely diagnosis.

Autoimmune hepatitis (AIH) is a relatively rare liver disease with varying worldwide incidence of from 0.7 to 2 per 100,000 people. It is characterized by the presence of auto-antibodies. However, an average of 10% of AIH cases have AIH symptoms and pathology but lack autoimmune serology. For such seronegative AIH (snAIH) cases, there is currently no established diagnostic algorithm for diagnosis. and improper or delayed diagnosis of snAIH can lead to no or inappropriate treatment that results in progression to fulminant hepatitis or cirrhosis. This review aims to review the current literature and to present an update of seronegative autoimmune hepatitis, including its pathophysiology, clinical presentation, methods of diagnosis, and treatment in order to increase awareness and emphasize the necessity for timely management.

In Tunisian folk medicine, several herbs are prescribed for reducing renal damage and to avoid kidney related complications. These can be of immense value in combating renal damage. In this review, we provide a description of the current literature on the use of indigenous herbs as alternative medicine for treating renal damage. The aim of this review was to collect information on promising active phytoconstituents such as organosulfur compounds, polyphenols, terpenes, alkaloids phenylpropanoids, and polysaccharides from Tunisian plants that have been scientifically examined for their nephroprotective capacities. Twenty-nine Tunisian medicinal plants have been reported for their significant nephroprotective activities against renal toxicities in animal models. Lamiaceae was the most commonly used Tunisian plant family used for renal protection. The leaves were maximally used for nephroprotection compared to the other plant parts. Nephrotoxicity is commonly the result of several nephrotoxins. Many studies have focussed on drug-caused renal failure which is one of the major problems in medical practice. Other studies focused on other important nephrotoxicity factors, including drugs and industrial chemicals. This literature review highlights the use of some medicinal plants as nephroprotective agents. To defend against this nephrotoxicity, some medicinal plants, known as nephroprotective agents, have been highlighted in this review.

Pancreatic adenocarcinoma (PAAD) is a common malignancy in the digestive tract. Emerging studies have reported that Bloom’s syndrome helicase (BLM) is closely associated with the tumor prognosis and immune microenvironment. Our study aimed to reveal BLM’s potential prognosis value in PAAD.

Potential oncogenic effects and prognostic influence of BLM were explored based on the TCGA and GETx databases. Gene mutation and methylation analyses were performed on the cBioPortal website and SMART database. The ARCHS4 and JASPAR2022 databases were used to predict the upstream transcription factor targets (TFs) of BLM. Starbase was used to explore the upstream ncRNAs. The relationship of BLM with the PAAD immune infiltration and immune checkpoints was analyzed using TIMER and GEPIA databases.

BLM was highly expressed and correlated with a poor prognosis in PAAD. The hypomethylation of BLM was observed in PAAD and correlated with a poor prognosis. The predicted TFs (E2F1 and ETS1) were also highly expressed and positively correlated with a poor prognosis in PAAD. LINC01133-miR-30b-5p axis was explored to be the most potential upstream ncRNAs of BLM in PAAD. Furthermore, the BLM expression was positively correlated with the PAAD immune infiltration cells. The BLM expression was also positively correlated with the expression of the immune checkpoints of PD1, PD-L1, CTLA-4, and CD47.

The high expression of BLM was associated with the poor prognosis of PAAD. In addition, a high BLM expression could facilitate the expression of the immune checkpoints in the immune infiltration cells, which would promote PAAD progression and affect its prognosis.