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.

The real target planned is the prevention of COVID-19 using natural treatment tools, other than medical drugs, together with the use of vaccines. Similar to various viruses that lead to upper respiratory diseases, SARS-CoV-2 most frequently enters the body through the nasal cavity and oral cavity. It has been stated that the Oscardia Ledovir Spray can form a mechanical barrier in the mucosa of the nasal and oral cavities, which are the points of entry of the SARS-CoV-2 virus in the body, preventing the bonding of the virus to the receptors, and inhibiting any virus it encounters through direct contact.

The present study serves as evidence for this treatment. The application of disinfectants in percentage formulations has been officially accepted by the World Health Organization to kill viruses, and this was used to compare its effectiveness with the Oscardia Ledovir Spray. The obtained new sample mixture was placed on a plate. In the course of the study, it was determined that the Oscardia Ledovir Spray has an effect mechanism similar to ethyl alcohol and disinfectants.

Since the Oscardia Ledovir Spray was found to have an effect mechanism similar to ethyl alcohol and disinfectants, this was considered as the preferred treatment approach. The results of the present clinical study revealed that this treatment approach is effective, particularly for SARS-CoV-2.

The Oscardia Ledovir Spray can be considered to provide both prophylactic and therapeutic benefits, thereby contributing to humanity in improving processes that range from simple infections to serious diseases. Furthermore, it was considered that this treatment can be used for both SARS-CoV-2, and viral and bacterial infections.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a global public health menace because of its immunopathogenesis and faster transmission than prior coronaviruses that infected people. Due to the genetic similarity between SARS-CoV and MERS-CoV infections, knowledge from earlier SARS-CoV and MERS-CoV infections has been used to infer the mechanism behind the host immune response during the infection with SARS-CoV-2 even though this knowledge is incomplete. The hyperactivation of macrophages and monocytes, which results in autophagic cell death and increases interleukin-6 and neutrophil levels, is evidence for this. It has been proposed that SARS-CoV-2 undermines the host’s immune system by blocking interferon induction and signaling, which contributes to a cytokine storm that may result in acute respiratory distress syndrome and multiple organ failure while reducing the host’s adaptive immunological responses. This work gives a broad review of the molecular dynamics of SARS-CoV-2 infection from the viewpoints of molecular biology, virology, and immunology in order to clarify and critically characterize the immunopathogenesis of SARS-CoV-2 and how it can alter sickness severity. Thus, this would enlighten us on potential new therapeutic avenues for future studies.

Radiation-induced pulmonary injury (RIPI) is a common adverse reaction when ionizing radiation acts on the lung. Type II alveolar epithelial cells participate in the process of RIPI by regulating inflammation, epithelial-mesenchymal transition, cellular senescence, etc. The expression of miR-139-5p is inhibited by ionizing radiation, which plays a role in modulating radiotherapy resistance in breast cancer tissues. PIEZO1, a mechano-sensitive ion channel, has been found to play an essential role in bleomycin-induced lung fibrosis. Moreover, there exist some common mechanisms between bleomycin-induced lung fibrosis and RIPI. The stretch changes during RIPI might also regulate PIEZO1 signaling. Furthermore, PIEZO1 is predicted to be a downstream target gene of miR-139-5p, and ionizing radiation leads to increased PIEZO1 mRNA and protein expression. We hypothesized that miR-139-5p might regulate PIEZO1 expression to modulate radiation-induced injury in type II alveolar epithelial cells. Therefore, it is of great practical significance to explore new ways to prevent and treat RIPI and break through the existing research bottlenecks for improving the prevention and treatment of RIPI.

Upper gastrointestinal tract cancer (UGIC), which includes both gastric and esophageal cancer, is a major threat to human health. Patients in the early stage have a significant chance to obtain a better prognosis, when compared to patients in the advanced stage. Improving the detection rate of early UGIC is important to improve the survival rate and prognosis. The endoscopic screening of UGIC includes opportunistic and population-based screening, and this has been carried out in a few regions. Compared to these two gastroscopy screening strategies, the early detection ability of opportunistic screening is no less than that for population-based screening, and the compliance of population-based participation is better. Considering economic factors, bundled opportunistic gastroscopy screening is cost-effective. Overall, the screening strategy for UGIC is limited by economic, medical and geographical factors, and the prospect of opportunistic screening is considerable.

Coronavirus disease 2019 (COVID-19), a global pandemic disease caused by SARS-CoV2 infection, has existed for nearly three years. However, there are currently only a few therapeutic drugs available. The objective of this study attempted to explore the potential therapeutic actions of Shuanghuanglian, a traditional Chinese medicine, using molecular docking simulation technology.

The ingredients of Shuanghuanglian and the approved drugs were structurally evaluated. The potential bindings of the individual ingredients in Shuanghuanglian to the PLPro and Mpro of the SARS-CoV2 were evaluated by molecular docking simulation according to the energy parameters. The corresponding binding patterns into each defined site were analyzed. The pharmacokinetics of the individual ingredients were predicted to preliminarily evaluate their oral bioavailability.

There were 482 unique natural products in the categories of fatty acids, aromatic compounds, glycosides, and sterols. The successfully docked rates of the Shuanghuanglian components binding to the PLPro and Mpro were all higher than those of the compounds in the Food and Drug Administration-approved Drug Library. In general, Shuang and Lian took the primary status in providing the top hits via the hydrogen bonds, while Huang acted as an important supplement to the global activity. Though the selected hits faced the common difficulty of polarity, the deglycosylation and the package by the carriers could also be practical to overcome the pharmacokinetic violation.

Shuang and Lian retain the potential ability to interact with the PLPro and Mpro of SARS-CoV2, and other herbs seem to have the potential to be involved.

Positive surgical margin (PSM) after radical prostatectomy (RP) is an established factor associated with the outcome of biochemical recurrence (BCR). Dominant tumor is presumed to harbor the most aggressive biological behavior. The aim of this study was to evaluate the clinical significance of the PSM laterality and its correlation with dominant tumor.

Excluding cases with multiple location PSM, 406 consecutive PSM patients after RP between 1993 and 2007 were retrospectively reviewed and included in this study. The BCR prognosis was estimated by the Kaplan-Meier survival analysis.

Of these 406 PSM cases, 115 cases (28.3%) had apex PSM, 272 cases (67.0%) had peripheral PSM, and 19 cases (4.7%) had bladder neck PSM. Among the 272 peripheral PSM cases, 117 cases (43.0%) were on the right side, 111 cases (40.8%) were on the left side, and 44 cases (16.2%) were on both sides of the prostate. For tumor dominancy, 87 cases (21.4%) were right dominant, and 70 cases (17.2%) were left dominant, whereas the remainder were non-laterality dominant. Similar clinicopathological and oncologic characteristics were observed between right and left PSM or dominant tumor. When compared to cases with same side PSM and dominant tumor, the cases with contralateral PSM to dominant tumor showed a significantly worse BCR prognosis in high-risk cases (p < 0.001).

Our results indicated that the laterality of both PSM and tumor dominancy did not have any clinical significance. However, the significantly worse BCR prognosis of cases with a contralateral PSM to dominant tumor in the high-risk cases may suggest a more aggressive invasion ability, but not only due to an anatomical oppressive growth.

Pancreatic cancer (PC) is one of the most dismal diseases with a five-year survival rate of only 6%. Such poor prognosis is attributed to both a lack of early detection methods and its intrinsic resistance to cytotoxic agents and radiotherapy. Identifying driving events in the initial stage is of great significance for curable pancreatic ductal adenocarcinoma (PDA) detection and effective targeted therapy. Furthermore, Kirsten rat sarcoma viral oncogene (KRAS) plays a critical role in the initiation and maintenance of pancreatic tumors, thus contributing to the conversion of anti-tumor inflammation to pro-tumor inflammation. Both the KRAS mutation and inflammation are concurrent in the initial stage of PDA, and they compose a positive feedback loop to enhance each other’s activity. This positive feedback loop generates a harsh environment, which helps pancreatic cells maintain the stemness phenotype, accelerates cell turnover rate, increases genome instability, and hence elevates the incidence of PDA formation.

Left ventricular thrombus (LVT) is a common complication of coronary heart disease; thus, traditional Chinese medicine has become a therapeutic option. Here we report two LVT cases treated with Western medicine and traditional Chinese herbal medicine. After treatment, the thrombus became obviously smaller than before, and the clinical symptoms were also relieved. Furthermore, there was little relevant literature in this field, so we expect that this report could support the efficacy of traditional Chinese medicine in treating LVT.

Selective androgen receptor modulators (SARMs) are a class of nonsteroidal drugs that are favored over anabolic androgenic steroids (AASs) for their tissue-selectivity and improved side-effect profile. These drugs have been evaluated for treatment of various diseases including muscle-wasting disorders, osteoporosis, and breast cancer. Despite lacking approval for therapeutic use, SARMs are widely used recreationally as performance enhancing drugs by bodybuilders and athletes. In recent years, cases of drug-induced liver injury (DILI) secondary to SARMs have begun to emerge, but little is known regarding their hepatotoxicity. In this review, we provide current knowledge regarding DILI from SARMs. A literature search was conducted regarding SARMs and liver injury to evaluate relevant cases and information. SARMs have been associated with a cholestatic syndrome congruent with that of DILI from AASs, and it consists of a bland cholestasis in which there is minimal bile duct injury, inflammation, or necrosis. Patients present with an insidious onset of jaundice with marked hyperbilirubinemia and mild hepatic enzyme elevations. No clear treatment exists, although patients typically show improvement with cessation of the offending SARM. Given the novelty of these drugs, further study is necessary to understand diagnosis, management, and complications of SARM-related DILI.

In this study we use vibrational optical coherence tomography (VOCT) to study the mechanovibrational peak heights exhibited by benign and cancerous skin lesions. When a tissue is vibrated using audible sound it resonates at frequencies that represent the major components. The resonant frequency is related to the elastic modulus through a calibration equation developed in vitro using isolated tissue components. New cancerous skin lesions were identified based on the presence of a new cellular peak (80 Hz) with increased stiffness, a new blood vessel peak (130 Hz) that appears to be less stiff than normal blood vessels (150 Hz), and a fibrous tissue peak (260 Hz) present in carcinomas. The objective of this study was to differentiate different skin cancers using VOCT.

Mechanovibrational spectra were normalized by dividing by the largest peak of the different skin lesions. Differences in peak heights between actinic keratosis, basal cell carcinoma, squamous cell carcinoma, and melanoma were used to noninvasively “fingerprint” the different skin lesions.

The results suggest that VOCT can be used to noninvasively differentiate between different skin cancers and to identify early skin cancers possibly as small as 0.1 mm based on the heights of the 50, 80, and 130 Hz peaks

Further work is underway to use machine learning in conjunction with quantitative VOCT peak heights derived from mechanovibrational spectra to noninvasively identify different skin cancers.

Tenofovir amibufenamide (TMF) is a novel phosphoramidated prodrug of tenofovir with noninferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate (TDF) in 48 weeks of treatment. Here, we update 96-week comparison results.

Patients with chronic hepatitis B were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks. The virological suppression was defined as HBV DNA levels <20 IU/mL at week 96. Safety was evaluated thoroughly with focusing on bone, renal, and metabolic parameters.

Virological suppression rates at week 96 were similar between TMF and TDF group in both HBeAg-positive and HBeAg-negative populations. Noninferior efficacy was maintained in the pooled population, while it was first achieved in patients with HBV DNA ≥7 or 8 log10 IU/mL at baseline. Non-indexed estimated glomerular filtration rate for renal safety assessment was adopted, while a smaller decline of which was seen in the TMF group than in the TDF group (p=0.01). For bone mineral density, patients receiving TMF displayed significantly lower reduction levels in the densities of spine, hip, and femur neck at week 96 than those receiving TDF. In addition, the lipid parameters were stable after week 48 in all groups while weight change still showed the opposite trend.

TMF maintained similar efficacy at week 96 compared with TDF with continued superior bone and renal safety profiles (NCT03903796).

Hes1 is the downstream target of the canonical Notch-signaling pathway, which plays an essential role in maintaining intestinal proliferative crypts and regulating enterocyte differentiation. Loss of Hes1 expression is frequently observed in right-sided colon cancers. This study aims to present the relationship between the dysregulated Notch pathway and the status of RAS or BRAF mutations.

Forty-three cases of primary colorectal adenocarcinomas were collected in a tertiary teaching hospital. Hes1 expression was assessed by the immunohistochemical stain. The RAS (KRAS and NRAS) and APC status were determined by the next-generation sequencing study. In addition, BRAF V600E was tested by PCR-based mutation analysis.

Overall, loss of Hes1 expression was observed more frequently in colorectal cancer specimens with either RAS or BRAF mutations than in the wild type (78.6% vs. 40.0%, p < 0.05). All the right-side tumors with RAS or BRAF mutations showed loss of Hes1 expression (12/12, 100%) (p < 0.05), compared to only 62.5% (10/16) of left-sided tumors. In addition, patients with Hes1 loss in tumor tissue were less likely to have immediate metastasis (59.1%, 13/22) compared to those with preserved Hes1 expression (83.3%, 5/6) (p = 0.37).

The high frequency of Hes1 loss in colorectal adenocarcinoma is associated with either RAS or BRAF mutations, suggesting that synergistic effects by dysregulated Notch and RAS/BRAF mutation might play a vital role in colon carcinogenesis in some forms, especially the right-sided tumors. This finding might help guide future treatments for a subset of colon cancers.