The intestinal microbiota is considered a large organ in the human body performing functions in the host that range from supporting digestion and absorption of nutrients from the diet to regulating the various processes in the host. Maintaining a diverse and stable microbiota is critical to maintaining host homeostasis and health. Studies have suggested the relationship between the microbial changes and the development of several pathologies. In this context, metformin, has shown to be a promising drug for the regulation of the microbiota, thus favoring the prevention and treatment of type 2 diabetes mellitus (T2DM), obesity, cancer, the inflammatory state of human immunodeficiency virus (HIV), heart disease, Alzheimer’s disease and aging, and pathologies associated with dysbiosis. In this review, the main aspects on the importance of metformin’s action on dysbiosis, and the factors that regulate the metformin uptake and activity as genetic polymorphisms and GLP-1 receptor activation were discussed.

Codiaeum variegatum (C. variegatum), which is commonly known as garden croton, is a medicinal plant used for the treatment of amoebiasis in Cameroon and some Asian countries. The present study aims to evaluate the antioxidant and anti-inflammatory activities of the stem crude extracts of C. variegatum.

Aqueous, hydroethanolic 70/30 (v/v) and ethanolic extracts (EE) were tested for antioxidant activity using 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging, ferric iron-reducing antioxidant power (FRAP), and lipid peroxidation inhibitory assays. The anti-inflammatory activity was determined based on the inhibition of nitric oxide (NO) production on isolated mouse macrophages activated by Saccharomyces cerevisiae. Furthermore, the inhibitory effect of these extracts on 5-lipoxygenase activity and bovine serum albumin (BSA) denaturation was determined, and the activation of two lysosomal enzymes involved in phagocytosis was performed. The phytochemical screening of the plant extracts was performed using standard methods for phenol, flavonoid, tannin, etc.

The results revealed that the EE exhibited the highest antioxidant activity, in terms of DPPH-free radical scavenging activity, FRAP, and its potential to inhibit lipid peroxidation (IC50 = 77.04 µg extract/mol of DPPH; EC50 = 543.6 µg/mL and IC50 = 21.52 µg/mL, respectively). However, this activity remained significantly lower than that of ascorbic acid (p < 0,05). Furthermore, the hydroethanolic extract (HE) had the highest anti-inflammatory activity on isolated mouse macrophages, in terms of inhibitory activity on NO production, BSA denaturation, and 5-lipoxygenase activity (IC50 = 8.80 µg/mL, IC50 = 205.9 µg/mL, IC50 = 0.08 µg/mL, respectively). However, there was no significant difference in the inhibitory activity of baicalin. Moreover, the activity of acid phosphatase and alkaline phosphatase increased in the presence of the HE (EC50 = 10.03 µg/mL and EC50 = 0.274 µg/mL, respectively). The phytochemical analysis of these extracts indicates the presence of phenolic compounds, and these may be responsible for the observed activities.

Overall, these results demonstrate that the hydroethanolic and ethanolic stem extracts of C. variegatum have good antioxidant and anti-inflammatory potential.

Chemotherapy-induced nausea and vomiting (CINV) are both common clinical problems in cancer patients. As a traditional Chinese medicine treatment method, acupuncture has a remarkable healing effect on the treatment of nausea and vomiting, but a systematic meta-analysis is lacking concerning this topic.

This paper searched the randomized controlled clinical trial literature on acupuncture for the prevention of CINV in the Pubmed, EMBASE, CNKI, WF (WAFANG DATE), Cochrane, and VIP (CQVIP) databases with a search date of October 20, 2021. An independent quality evaluation and effect size extraction of the literature were performed by two researchers, and the meta-analysis and quality evaluation of all the literature was performed using RevMan 5.4. A total of 18 publications meeting the criteria were screened for the meta-analysis with a total of 1,135 patients.

Combined acupuncture prophylaxis was significantly better than other chemotherapy regimens in comparison with conventional chemotherapy regimens (risk ratio (RR) = 1.29; 95% confidence interval (CI): 1.17–1.43, p < 0.00001; odds ratio (OR) = 3.61; 95% CI: 2.19–5.96, p < 0.00001). Combined acupuncture was also effective in the prevention of side effects, such as loss of appetite (RR = 0.64; 95% CI:0.42–0.97, p < 0.00001; OR = 0.52; 95% CI:0.28–0.96, p = 0.04), constipation (RR = 0.57; 95% CI :0.44–0.73, p < 0.00001; OR = 0.30; 95% CI:0.18–0.51, p < 0.00001), and diarrhea (RR = 0.58; 95% CI:0.39–0.86, p < 0.00001; OR = 0.31; 95% CI:0.13–0.72, p < 0.00001).

Acupuncture prevention could reduce the incidence of CINV which has certain research value and thus would be worthy of research trials and clinical application.

Hepatic stellate cells (HSCs) play an essential role in various liver diseases, and exosomes are critical mediators of intercellular communication in local and distant microenvironments. Cellular crosstalk between HSCs and surrounding multiple tissue-resident cells promotes or inhibits the activation of HSCs. Substantial evidence has revealed that HSC-derived exosomes are involved in the occurrence and development of liver diseases through the regulation of retinoid metabolism, lipid metabolism, glucose metabolism, protein metabolism, and mitochondrial metabolism. HSC-derived exosomes are underpinned by vehicle molecules, such as mRNAs and microRNAs, that function in, and significantly affect, the processes of various liver diseases, such as acute liver injury, alcoholic liver disease, nonalcoholic fatty liver disease, viral hepatitis, fibrosis, and cancer. As such, numerous exosomes derived from HSCs or HSC-associated exosomes have attracted attention because of their biological roles and translational applications as potential targets for therapeutic targets. Herein, we review the pathophysiological and metabolic processes associated with HSC-derived exosomes, their roles in various liver diseases and their potential clinical application.

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.

Non-alcoholic fatty liver disease (NAFLD) has become the world's most common chronic liver disease and is considered one of the main causes of occult liver cirrhosis. To date, major guidelines in China and abroad have not recommended any drugs with precise efficacy and safety for NAFLD, especially for NAFLD-related liver fibrosis or cirrhosis, which lack effective drugs. Traditional Chinese medicine has significant curative effects and advantages in preventing and treating NAFLD. We retrospectively analyzed a case of liver cirrhosis due to NAFLD that was treated solely with traditional Chinese medicine for nearly one year at the Diagnosis and Treatment Center of Advantage Specific Diseases for Fatty Liver in our hospital to provide a reference for the prevention and treatment of non-alcoholic liver fibrosis and liver cirrhosis by traditional Chinese medicine.

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.

Colorectal cancer has high morbidity and mortality rates; therefore, developing new therapeutic drugs and methods for it is crucial. There is increasing evidence that intestinal flora plays a vital role in maintaining intestinal homeostasis and therefore, in the development of colorectal cancer. As such, therapeutic approaches using probiotics such as Bifidobacterium lactis to regulate intestinal flora are expected to represent a new treatment strategy for colorectal cancer. This article introduces and compares the development status of conventional therapies for colorectal cancer, primarily targeted therapy and immunotherapy, the relationship between intestinal flora and colorectal cancer, and the research and application of Bifidobacterium bifidum in colorectal cancer treatment to provide a reference for its clinical application.

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.

Functional dyspepsia (FD) is a regularly diagnosed clinical gastrointestinal ailment with a high incidence rate that can considerably impact patients' health and quality of life and impose a substantial financial burden. Modern research on the pathophysiology of functional dyspepsia has not thoroughly explained the underlying reasons. The condition does not manifest any significant organ abnormalities, which raises the disease's difficulty coefficient. Major pathogenic exceptions in FD include gastrointestinal motor dysfunction, gastrointestinal hormone secretion problem, visceral hypersensitivity, and brain-gut axis. Several ion channels have reportedly been implicated in the pathophysiological process of FD. Therefore, it is crucial to comprehend the probable activities of various ion channels in FD. This study focuses on the current state of research on the possible role of several ion channels in the pathogenesis of FD.