Age-related macular degeneration (AMD) is difficult to treat and causes visual impairment worldwide, especially for dry AMD. The aging phenomenon can affect macular function, manifesting as blurred central vision. There are two types of AMD: dry and wet. By 2040, some variants of AMD are estimated to affect 288 million people globally. Although wet (exudative) AMD accounts for 10% of all AMD cases, it also contributes to 90% of the cases of patients with vision loss. Therapeutic options for wet age-related macular degeneration have expanded during the last few years. The therapeutic strategies mainly rely on anti-vascular endothelial growth factor (anti-VEGF) drugs and photodynamic therapy (PDT), though the treatment approaches for dry AMD are limited to dietary supplementation to delay progression. Moreover, clinical trials with potential candidate molecules for wet AMD exceed those for dry AMD. Although the disease is not rare, there are few therapeutic targets in the pipeline for dry AMD, and these targets may serve as promising pharmacotherapeutic options in the future. The current review sheds light on successes and failures of the existing novel drug molecules and potential targets for treating dry AMD in clinical trials registered at the Clinical Trials.gov registry run by the United States Food and Drug Administration (U.S. FDA) and published in relevant journals.

Primary biliary cholangitis (PBC) has been shown to occur more often in the West than in the East. The reason for this geographical disparity remains to be determined. Some researchers have considered that this was merely due to the lack of awareness on PBC in the East. Thus, the reported case and epidemiological studies on this disease remain scarce in the East. Other studies have suggested genetic predisposition and environmental factors proven to play important roles in the disease pathogenesis. In addition, these might also cause the disease to be more susceptible in some populations. The findings reported by multiple genome-wide association studies (GWAS) in recent years have not yet identified the specific genes responsible for the development of PBC, with different susceptible genes identified on each study in different regions. The present review describes some factors that might be associated with this geographical disparity.

Primary biliary cholangitis (PBC) is an organ-specific chronic autoimmune disease characterized by T-lymphocyte mediated destruction of intrahepatic biliary epithelial cells due to a combination of genetic and possible environmental factors. PBC progresses to hepatic fibrosis and cirrhosis, with the potential of developing hepatocellular carcinoma (HCC) if left untreated. PBC is more common in middle-aged women. It is diagnosed in patients with elevated liver enzymes and the serological hallmark of antimitochondrial antibody (AMA). Early diagnosis and treatment are crucial in improving survival and preventing long-term complications of liver disease. Ursodeoxycholic acid (UDCA) is first-line treatment for PBC. Obeticholic acid (OCA) and fibrates, in combination with UDCA or as monotherapy, may be given to PBC patients with partial or no UDCA response. Liver transplantation has thus been indicated in patients with decompensated cirrhosis or unresectable HCC.

In-stent restenosis (ISR) is a common complication after percutaneous coronary intervention. This study aimed to investigate the mechanisms of Radix Salviae in preventing ISR based on network pharmacology.

The bioactive compounds were searched from natural product databases. The related targets were collected from the databases and screened. The drug-compound-target-disease network was then constructed by Venny and Cytoscape software, and the intersection targets were further investigated in the STRING database. Functional enrichment analysis was performed in the DAVID database by conducting gene ontology and Kyoto Encyclopaedia of Genes and Genomes analyses. The software AutoDock Vina was used to conduct the molecular docking simulation.

A total of 33 bioactive compounds, including Luteolin, Tanshinone iia, and Dihydrotanshinlactone of Radix Salviae, were predicted with 53 targets as the compound-related targets in the ISR disease. Then the protein-protein interaction analysis discovered three key nodes, i.e., STAT3, JUN, and TP53. Moreover, functional enrichment of the gene ontology analysis demonstrated that the main biological processes included the response to the drug and regulation of the transcription from the RNA polymerase II promoter. The main molecular functions included protein binding, etc. The Kyoto Encyclopaedia of Genes and Genomes analysis revealed that the signaling pathways were mainly related to the PI3K-Akt signaling pathway, lipid-atherosclerosis signaling pathway, etc. Further investigation by molecular docking simulation between the ligands of the Radix Salviae compounds and target proteins revealed great probability binding activities between Luteolin-STAT3 (−7.4 kcal/mol), Tanshinone iia-TP53 (−7.2 kcal/mol), and Luteolin-TP53 (−6.2 kcal/mol).

This study indicated that the bioactive compounds like Tanshinone in Radix Salviae could modulate ISR via PI3K-Akt and lipid-atherosclerosis pathways, and the targets probably included STAT3, JUN, and TP53.

Congenital absence of the anterior cruciate ligament (ACL) is an extremely rare condition associated with a wide spectrum of malformation. Here we describe a rare complication in a patient with congenital absence of the ACL after ACL reconstruction using a bioabsorbable screw. A 35- year-old woman presented a right knee mass that had been slowly growing for several months. Five years previously, she experienced acute right knee pain, locking, and instability after hiking. Images and diagnostic arthroscopy at that time revealed an absence of the anterior cruciate ligament, a hypoplastic lateral distal femoral condyle, a stenotic intercondylar notch, and hypoplastic posterior cruciate ligament along with a bucket handle tear of the medial meniscus. A right anterior cruciate ligament reconstruction was performed, and she did well for the next five years without knee joint instability until she presented a mildly painful subcutaneous pretibial soft tissue mass. Imaging studies demonstrated a 2.4 cm subcutaneous lobulated soft tissue mass protruding from the expanded tibial tunnel. The mass was excised, and the histology showed a solid and cystic lesion composed of a histiocytic and foreign body giant cell reaction to the degraded polymer along with spheres of calcium phosphate particles. At a two-year follow-up after debridement, the patient reported an overall improvement without any knee instability or local recurrence. To the best of our knowledge, this is the first report of a pseudotumor developed after ACL reconstruction in a patient with a congenital absence of the ACL.

Despite its short length, the anal canal is an anatomically and histologically complex organ that can harbor many benign and malignant conditions. The trend for anal cancer has been on the rise, affecting predominantly women. In recent years, new concepts have emerged regarding anal tumor origin, pathogenesis, classification, and molecular characterization. Particularly, the role of human papillomavirus (HPV) has been increasingly recognized for its important role in anal carcinogenesis, not just for squamous lesions, but also for non-squamous neoplasia. Understanding different mechanisms of tumorigenesis are essential for proper tumor classification, which will allow more accurate diagnosis, proper clinical management, and optimal patient outcomes. This review aims to provide an overview of the normal anatomy, histogenesis, and pathogenesis of the anal canal, as well as to update on current knowledge of epithelial tumors associated with HPV.

Asthma has become a serious global public health issue affecting approximately 14% of children worldwide. Asthma patients often accompany various mental disorders, such as depression, anxiety, and panic attacks, which could aggravate asthma symptoms. It can be summarized that in addition to pathological cellular and molecular immune processes, asthma also has a neural phenotype. The first part of this review summarizes the prevalence and economic burden of asthma in recent years. Then, the neurophenotype of asthma is described in terms of brain structural changes, molecular expression, and prevalence. Our literature search shows that the frontal lobe plays an essential role in asthma-related neurophenotypes. Finally, we assume that an electroencephalogram signal could be one of the directions of asthma neurophenotype diagnosis.

Today, medicinal plants and phytobiotics that contain flavonoids, alkaloids, and essential oils are widely used in animal feed. These additives have many benefits, including increasing liver function and preventing certain diseases. The liver is one of the organs that plays a key role in insulin-mediated regulation of metabolism as well as in glucose, whole-body, and lipid homeostasis. The aim of this study was to investigate the effect of fennel (Foeniculum vulgare) seed powder consumption on insulin-like growth factor 1 (IGF1) gene expression in the liver tissue of growing lambs.

Three groups (including 0, 10, and 20 g/kg dry matter of fennel) of animals, with 10 animals in each group, were studied. The Pfaffl method was applied to assess the real-time polymerase chain reaction (qPCR) output.

Mixing fennel into the feed of lambs increased the weights of their testis and gallbladder and decreased the weight of their liver in comparison to feed without fennel. It was also found that by increasing the fennel level in the feed, the expression level of IGF1 in the liver increased significantly (p < 0.05).

Fennel has a useful effect on the expression of IGF1 in the liver tissue of sheep and may be applied to their diet to attain better liver function.

Liver cancer is one of the most common malignant solid organ tumors. This cancer is associated with a high death rate. At present, it is possible to investigate a functional dysfunction module of hepatocellular carcinoma (HCC) using the genetic characteristics of liver tissue, revealing its pathogenesis and guiding tailored management and therapy. It not only provides important information for additional diagnostic therapy but also offers new research directions for scientists and medical technologists studying liver cancer.

Gastric cancer (GC) is one of the most common malignancies, but research on it is still limited. The role of immuntonic cell death (ICD)-associated long non-coding RNA (lncRNA) in GC is still unclear. Therefore, this experiment aimed to investigate the role of ICD-related lncRNA in GC, its prognostic value, and immunotherapeutic potential.

In this study, the relevant data were obtained from The Cancer Genome Atlas database. We used Pearson correlation coefficient analysis to obtain the ICD-related lncRNA, and randomly divided the data into the test and training groups in a 1:1 ratio. Then, we used Cox regression analysis and Lasso regression analysis to build a prognostic model. The receiver operating characteristic (ROC) curve was applied to analyze its accuracy, and immunocorrelation analysis was also performed for GC.

In this study, nine lncRNAs were selected to construct a prognostic feature, comprising AC005332.1, AC116312.1, LINC00705, CEP250-AS1, AC234775.2, LINC01150, FLJ16779, UBL7-AS1, and AC010457.1. The result of the ROC curve proved the reliability of its feature. The concurrently constructed features could be used as independent variables for a variety of clinical conditions. The analysis of the immune-related functions showed that there were differences in some immune functions between the high-risk and low-risk groups. We also found that the high-risk group was more sensitive to immunotherapy.

Based on the analysis of the ICD-related lncRNA in GC, our immune-related predictions and model could help predict the outcome of GC and could provide a reference for clinical practice.

In the US, about 14.5 million people ages 12 and older suffered from alcohol use disorder (AUD) in 2019. AUD affects multiple systems and is a major cause of disability and morbidity, severely reducing quality of life. With currently available pharmacotherapy and psychotherapy (including behavioral therapy) relapse rates remain high due to poor patient acceptability as well as the added factor of craving and impulsivity in addiction disorders. This points to the development of therapies that also act on functional areas of brain responsible for craving and impulsivity. Transcranial magnetic stimulation (TMS) is one type of neuromodulation under study for the treatment of AUD. Here, we review the work done on TMS as a treatment for AUD.

We searched PubMed and Cochrane databases for relevant articles with the main search terms of “transcranial magnetic stimulation” and “alcoholism”.

Most studies involve stimulation of right dorsolateral prefrontal cortex. Majority demonstrate a decrease in craving but only over time, not between groups. Overall, studies using TMS for the treatment of AUD show mixed results in changes in craving, impulsivity, and alcohol intake.

Mainly, the studies are limited by sample size and lack of uniformity in outcomes measured. Significance of TMS for treatment of AUD is still not clear. A standardized protocol of investigation is needed to allow for a meta-analysis to calculate the overall effect.

Oxaliplatin is widely used in cancer chemotherapy with adverse effects such as liver toxicity. Magnesium isoglycyrrhizinate (MgIG) has hepatoprotective effects, but the underlying mechanism remains elusive. The study’s aim was to investigate the mechanism underlying the hepatoprotective effects of MgIG against oxaliplatin-induced liver injury.

A xenografted colorectal cancer mouse model was established with MC38 cells. Mice were given oxaliplatin (6 mg/kg/week) for 5 weeks to mimic oxaliplatin-induced liver injury in vivo. LX-2 human hepatic stellate cell s(HSCs) were employed for in vitro studies. Serological tests, hematoxylin and eosin staining, oil red O staining and transmission electron microscopy were used for histopathological examinations. Real-time PCR, western blotting, immunofluorescence and immunohistochemical staining were used to determine Cx43 mRNA or protein levels. Flow cytometry was used to assay reactive oxygen species (ROS) and mitochondrial membrane. Short hairpin RNA targeting Cx43 was lentivirally transduced in LX-2 cells. Ultra-high performance liquid chromatography-tandem mass spectrometry was used to determine MgIG and metabolite concentration.

MgIG (40 mg/kg/day) treatment significantly reduced serum aspartate transaminase (AST) and alanine transaminase (ALT) levels in the mouse model, and alleviated liver pathological changes, including necrosis, sinusoidal expansion, mitochondrial damage, and fibrosis. MgIG reduced the abnormal expression of Cx43 in the mitochondria and nuclei of HSCs. MgIG inhibited the activation of HSCs via reducing ROS generation, mitochondrial dysfunction, and N-cadherin transcription. MgIG’s inhibition of HSCs activation was abolished after knockdown of Cx43 in LX-2 cells.

Cx43 mediated MgIG’s hepatoprotective effects against oxaliplatin-induced toxicity.

Early identification of prognostic factors to predict transplant/death outcome of biliary atresia (BA) is challenging. We aimed to investigate the longitudinal changes and predictive value of dynamic changes in acoustic radiation force impulse elastography with shear wave speed (SWS) quantification and other parameters within three months after hepatoportoenterostomy (HPE) for 2-year BA outcomes.

Seventy-four patients who underwent HPE between July 2016 and June 2019 were prospectively enrolled. Outcomes were classified into native liver survival and transplant/death groups. Acoustic radiation force impulse elastography was performed sequentially at 3 months intervals post-HPE. Cox regression analysis was used to determine the superior SWS values and other predictors of liver transplantation or death.

Among patients 2 years of age, 36 survived with a native liver, nine died, and 29 underwent liver transplantation. The trend in SWS levels in the transplant/death group was significantly different from that in the native liver survival group. ΔSWS at 1–3 months post-HPE and total bilirubin at 1 month post-HPE were selected as superior predictors of liver transplantation or death using multivariate Cox regression models: hazard ratio (HR)=1.927; 95% confidence interval (CI): 1.475–2.661; p<0.001 and HR=1.010; 95% CI: 1.003–1.017; p=0.007, respectively. The combination of the selected ΔSWS and total bilirubin had good predictive power, with an area under the receiver operating characteristics curve of 0.89, specificity 94.44% and sensitivity 73.68%.

Our results suggest that early postoperative bilirubin levels and SWS changes were reliable predictors of 2-year BA outcomes.

Cannabis has a long history of use in treating human diseases, but scientific research on its properties has only recently gained momentum. The increasing prevalence of antibiotic resistance in human and animal pathogens has sparked renewed interest in exploring alternative antimicrobial therapies from Cannabis and other plant sources. There is also potential for Cannabis extracts or purified cannabinoids to be applied in novel medical contexts. Industrial hemp extracts may find applications in food manufacturing, veterinary purposes, and microbial control in cleaners and sanitizers. This review highlights the latest discoveries regarding Cannabis plant extracts and phytochemicals as potent antimicrobial agents against various microorganisms, including Gram-positive and Gram-negative bacteria. More importantly, the challenges of using cannabinoids as effective and affordable natural antimicrobial agents are reviewed. While antimicrobial and other applications of Cannabis extracts and phytochemicals appear promising, concerns about possible toxic side effects exist. Therefore, future research should focus on addressing the safety of these compounds, evaluating their in vivo activity, and understanding structural changes that influence their pharmacokinetic properties. Standardized tests will be crucial for facilitating valid inter-laboratory comparisons. The review article also discusses future research directions aimed at developing novel broad-spectrum antibiotics based on Cannabis.

Primary biliary cholangitis (PBC), which is formally known as primary biliary cirrhosis, is a progressive chronic cholestatic liver disease. Previous epidemiologic studies have demonstrated female predominance. Furthermore, the pathophysiology of PBC is multifactorial, and involves loss of immune tolerance to biliary epithelial cells, with interdependent biliary injury, cholestasis, and progressive liver fibrosis. Moreover, its progression to liver fibrosis highly varies among individuals, but most cases are indolent and slowly progressive. Over the past decade, research has provided great insight into personalized care for patients with PBC. Individualized care and early utilization of second- and third-line therapies have improved the outcomes, and decreased the progression of this disease. The present mini-review focus on providing an overview of PBC, including its pathophysiology, clinical presentation, treatment, treatment goals, recommended follow-up, and future research.