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221
Review Article Open Access
Indre Zaparackaite, Shailinder Jit Singh, Debashish Bhattacharya, Swamy Kaki Bale, Rafael Cavalcante Correia, Partap Kumar Midha, Dhaval Govani, Ramnik Vallabh Patel
Published online September 10, 2024
Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00092
Abstract
Based on our experimental and clinical research, the gastroschisis is formed by raised intraluminal and intraabdominal pressure in combination with potential weak points. The psycho-neuro-endocrine-target [...] Read more.

Based on our experimental and clinical research, the gastroschisis is formed by raised intraluminal and intraabdominal pressure in combination with potential weak points. The psycho-neuro-endocrine-target organ axis of young mothers, who themselves struggle to meet their macro and micronutrient requirements, places a burden on the placenta. The associated smoking, alcohol, drugs, and other toxins, leads to fetal distress. This activates the same fetal axis, with the final common pathway being activated via the sacral parasympathetic nervous system as a flight or fight response leading to colorectal secreto-motility disorder of the hindgut and small left colon leading to partial functional obstruction of hindgut. This leads to pressure build-up on the proximal colon. An intact ileocecal valve leads to blind loop obstruction, creating the force required to herniate the bowel through the defect at three key points of weakness in the abdominal wall, the most vulnerable being the right paraumbilical region. If the ileocecal valve becomes incompetent, variants of gastroschisis may occur. The fetus, particularly the peritoneum, always has a tendency to heal defects quickly, which forms secondary events in the eviscerated bowel causing the closing and closed gastroschisis with vanishing organs. Recent technological advances in preformed silastic silo innovation, prenatal diagnosis and monitoring for closing gastroschisis, perinatal management, percutaneous central long lines, and innovative minimally invasive bedside procedures, have all made significant contributions. We believe that gastroschisis is the external surgical symptom and peak of the iceberg, secondary to an underlying colorectal motility disorder, providing the force to eviscerate bowel loops through potential weak points and its subsequent sequelae.

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222
Review Article Open Access
Yining Li, Chengxiang Zhou, Tao Liu, Qiuling Xu
Published online September 6, 2024
Future Integrative Medicine. doi:10.14218/FIM.2023.00088S
Abstract
In recent years, global warming has led to regionally high temperatures, causing lasting and extreme impacts in some areas of China. Cases of heat stroke and even fatalities have [...] Read more.

In recent years, global warming has led to regionally high temperatures, causing lasting and extreme impacts in some areas of China. Cases of heat stroke and even fatalities have been seen in many parts of the country. Traditional Chinese medicine considers heat stroke to be a type of summerheat stroke, which belongs to the extreme heat of the Yang. Bloodletting therapy is a classical treatment in traditional Chinese medicine. Bloodletting involves puncturing certain acupoints or small epidermal veins to release a small amount of blood to dredge the channel and clear heat-fire, thus lowering a patient’s body temperature. Therefore, studying bloodletting therapy as a treatment for heat stroke has significance. Here, we analyzed the core acupoint prescriptions and the application characteristics of bloodletting therapy for the treatment of heat stroke. Our review provides a basis for the selection of acupoints and treatment methods for the clinical use of bloodletting therapy for heat stroke.

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223
Review Article Open Access
Alla Turshudzhyan, Dana Gornick, Giuliana Mertz, Micheal Tadros
Published online September 6, 2024
Journal of Translational Gastroenterology. doi:10.14218/JTG.2024.00011
Abstract
Gastrointestinal endoscopy has undergone significant transformation since its first introduction in the early 20th century. Despite advances in modern endoscopy, its precision in [...] Read more.

Gastrointestinal endoscopy has undergone significant transformation since its first introduction in the early 20th century. Despite advances in modern endoscopy, its precision in detecting and removing colorectal cancer (CRC) varies; colorectal polyps or cancer are still missed in 2.1-5.9% of cases. Additionally, post-colonoscopy CRC occurs in 30% of patients who have undergone incomplete polyp resection. When biopsies are taken, only 11.4% are found to be malignant, rendering 88.6% of tissue removal unnecessary. To address these shortcomings, modern endoscopy is evolving. Current endoscopic modalities include wide-field and microscopic-field endoscopy. Wide-field view endoscopy remains the most frequently used type and includes the current standard of practice—white light endoscopy—as well as other modalities such as virtual and dye-based chromoendoscopy, ultrathin endoscopy, and capsule endoscopy. Microscopic field endoscopy encompasses several new emerging modalities that can provide microscopic resolution capable of diagnosing lesions in vivo (optical biopsy), thus reducing the number of unnecessary biopsies. However, the emerging technology comes with a learning curve and requires time for endoscopists to master and achieve interobserver agreement. Consequently, there is a growing opportunity to develop machine learning technology to assist with the learning process. We review current modalities available for the diagnosis of CRC, including the current standard of practice, new enhanced imaging modalities, and optical biopsy.

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224
Original Article Open Access
Jeremiah Onubi, Oluwagbenga Adebayo Adeola, Patricia Eseigbe, Adesegun Elisha, Grace O Sheyin, Anyuku A George Chima
Published online September 6, 2024
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00018
Abstract
Depression can lead to poor outcomes during antiretroviral therapy, and current evidence suggests high rates of depression among people living with human immunodeficiency virus [...] Read more.

Depression can lead to poor outcomes during antiretroviral therapy, and current evidence suggests high rates of depression among people living with human immunodeficiency virus (PLHIV), especially in low-and middle-income countries. This study was designed to investigate the sociodemographic factors associated with depression among PLHIV on antiretroviral therapy in a Nigerian cosmopolitan city.

A hospital-based, cross-sectional study was conducted among 592 consenting, randomly selected adult PLHIV receiving treatment at a university teaching hospital in Jos, Nigeria, in 2022, using the PHQ-9 questionnaire and an interviewer-administered sociodemographic questionnaire. Associated variables in univariate analysis were used in multivariable binary logistic regression to obtain adjusted odds ratios (AOR) with a significance level set at α = 0.05.

Depression was found to be highly prevalent among study participants, with 44.9% of them affected. Findings revealed that being male [AOR = 0.62; 95% confidence interval (CI): 0.42–0.92], being employed (AOR = 0.55; 95%CI: 0.31–0.97), and earning a monthly income of ₦50,000–100,000 ($65–130) (AOR = 0.49; 95% CI: 0.27–0.91) and >₦100,000–200,000(>$130–260) (AOR = 0.33; 95% CI: 0.13–0.77) were significantly associated with reduced odds of depression.

The significant association of being male, having formal employment, and earning a moderate monthly income with reduced odds of depression may have implications for policy and strategies for managing mental health issues among PLHIV in cosmopolitan areas like Jos, which face peculiar challenges such as cultural tensions, traffic congestion, and gentrification. PLHIV categories with a relatively higher likelihood of depression may benefit from targeted mental health support systems, in addition to other mental health management strategies generally available to PLHIV.

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225
Original Article Open Access
Yunfan Wang, Xuejia Qi, Mengting Zuo, Zhaoying Liu
Published online September 5, 2024
Future Integrative Medicine. doi:10.14218/FIM.2024.00029
Abstract
Gelsemium elegans Benth (G. elegans) is a traditional medicinal plant; however, it is highly toxic, and toxicity varies significantly between species. The cause of this difference [...] Read more.

Gelsemium elegans Benth (G. elegans) is a traditional medicinal plant; however, it is highly toxic, and toxicity varies significantly between species. The cause of this difference has not been clarified. Humantenirine is an important toxic alkaloid in G. elegans, and its metabolism has been poorly studied. This study aimed to compare the different metabolites formed by human liver microsomes, pig liver microsomes, and goat liver microsomes.

High-performance liquid chromatography/quadrupole time-of-flight mass spectrometry was used to study the metabolism of humantenirine in human liver microsomes, pig liver microsomes, and goat liver microsomes.

A total of eight metabolites (M1-M8) were identified, and three major metabolic pathways were found: demethylation (M1), dehydrogenation (M2, M3, M7), and oxidation (M4, M5, M6, M8).

Based on these results, it is hypothesized that demethylation is the major detoxification pathway for humantenirine, providing important information to better understand the metabolism and toxicity differences between species of G. elegans.

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226
Review Article Open Access
Ruwini Nishadini Senarathne, Banukie Nirosha Jayasuriya, Shehara Lakchani Abeysinghe Gunawardana
Published online September 3, 2024
Future Integrative Medicine. doi:10.14218/FIM.2024.00024
Abstract
A mental disorder, also referred to as a psychiatric disorder or mental illness, is characterized by significant disturbances in an individual’s thinking, emotions, or behavior. [...] Read more.

A mental disorder, also referred to as a psychiatric disorder or mental illness, is characterized by significant disturbances in an individual’s thinking, emotions, or behavior. In Ayurveda, herbal plants are used as alternative therapies for various ailments, including mental disorders. This review aims to provide a comprehensive overview of herbal medicines used in treating mental disorders in Sri Lanka. It relies on foundational books as primary sources to systematically identify and analyze the therapeutic potential of 24 traditional medicinal plants for treating mental disorders. Each plant was evaluated based on its scientific name, plant parts used, distribution in Sri Lanka, mechanisms of action, and identified phytochemicals. Furthermore, additional research was conducted using keywords such as mental disorders, herbal plants, plant distribution, phytochemicals, side effects, and mechanism of action through scientific databases. The phytochemicals present in these herbal plants possess antioxidant, anti-inflammatory, and neuroprotective properties, contributing to their potential antipsychotic activities. Trigonelline (from Abrus precatorius), bacosides (from Bacopa monnieri), asiaticoside and asiatic acid (from Centella asiatica), quercetin (from Ginkgo biloba), alliin and allicin (from Allium sativum), luteolin-7-O-glucoside (from Eclipta alba), and shogaol (from Zingiber officinale) demonstrate significant potential in modulating neurotransmitter levels, reducing oxidative stress, and alleviating symptoms associated with mental disorders such as depression, anxiety, and neurodegenerative diseases. The suggested therapeutic value of these identified herbal plants and their bioactive phytochemicals indicates the need for preserving and extensively investigating these remedies to establish their clinical effectiveness.

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227
Review Article Open Access
Xiaoxi Feng, Rutong Zhang, Zhenye Yang, Kaiguang Zhang, Jun Xing
Published online September 3, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00019
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, has a high global prevalence and can progress to metabolic [...] Read more.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, has a high global prevalence and can progress to metabolic dysfunction-associated steatohepatitis, cirrhosis, and hepatocellular carcinoma. The pathogenesis of MASLD is primarily driven by disturbances in hepatic lipid metabolism, involving six key processes: increased hepatic fatty acid uptake, enhanced fatty acid synthesis, reduced oxidative degradation of fatty acids, increased cholesterol uptake, elevated cholesterol synthesis, and increased bile acid synthesis. Consequently, maintaining hepatic lipid metabolic homeostasis is essential for effective MASLD management. Numerous novel molecules and Chinese proprietary medicines have demonstrated promising therapeutic potential in treating MASLD, primarily by inhibiting lipid synthesis and promoting lipid oxidation. In this review, we summarized recent research on MASLD, elucidated the molecular mechanisms by which lipid metabolism disorders contribute to MASLD pathogenesis, and discussed various lipid metabolism-targeted therapeutic approaches for MASLD.

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228
Review Article Open Access
Megh R. Goyal, Anamika Chauhan
Published online September 2, 2024
Future Integrative Medicine. doi:10.14218/FIM.2023.00089
Abstract
In recent years, there has been a notable shift towards a holistic approach to human health, recognizing the importance of integrating essential nutrients with traditional natural [...] Read more.

In recent years, there has been a notable shift towards a holistic approach to human health, recognizing the importance of integrating essential nutrients with traditional natural medicines. This review article examines the potential synergy between nutrition and traditional healing practices in promoting well-being and disease prevention. It explores the diverse landscape of traditional medicine systems worldwide, highlighting their cultural significance and accumulated wisdom over generations. Moreover, it sheds light on the scientific foundations of these traditional remedies, showcasing their relevance in modern healthcare. Traditional natural medicines, often sourced from plants, animals, or minerals, offer a wide array of therapeutic options addressing root causes rather than symptoms alone. This enduring wisdom has sparked interest in complementing modern healthcare with traditional practices, aiming for a harmonious integration of tradition and evidence-based medicine. Furthermore, the article underscores the critical role of nutrients in maintaining overall health and preventing chronic diseases. It emphasizes the holistic perspective of health, encompassing mental, emotional, and physical well-being. The relationship between nutrition and health is also explored, emphasizing the importance of a balanced diet. The synergy between traditional natural medicines and nutritional interventions presents a promising avenue for a comprehensive approach to healthcare. The article advocates for collaborative research, interdisciplinary dialogue, and cross-cultural exchanges to harness the collective wisdom of the past and present. By embracing both nutrients and traditional medicines, we can move towards achieving optimal health and wellness, recognizing the profound interconnectedness between humans and the natural world.

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229
Case Report Open Access
Maxwell M. Chait, Naveed A. Chaudhry
Published online September 2, 2024
Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00076
Abstract
A colouterine fistula is an extremely rare condition that has been reported in various diseases, including diverticulitis, sigmoid colon malignancy, and complications from radiotherapy. [...] Read more.

A colouterine fistula is an extremely rare condition that has been reported in various diseases, including diverticulitis, sigmoid colon malignancy, and complications from radiotherapy. It can also arise from iatrogenic conditions such as the insertion of intrauterine devices, endometrial curettage with urinary tract and bowel perforation, and obstetrical injury. Although colovaginal fistula caused by a foreign body has been reported, colouterine perforation by a foreign body has not been previously documented. We report the first case of foreign body colouterine perforation and its successful treatment by endoscopic removal and repair, resulting in the complete resolution of symptoms without the need for surgery. This case is highly significant due to its rare occurrence and successful treatment by endoscopic removal and repair without the usual and expected necessity for surgical intervention.

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230
Original Article Open Access
Xing Liu, Fengyang Chen, Zhaozhe Liu, Mingyu Duan, Ye Gu, Xuan Liang, Xiaofeng Wu, Cheng Lv, Xinyue Li, Jiamin Qian, Meiyuxi Li, Linge Zhang, Tianyue Chen, Yan Wang, Guoliang Chen
Published online August 30, 2024
Future Integrative Medicine. doi:10.14218/FIM.2024.00022
Abstract
Albumin is a major prognostic factor for patients with advanced liver disease, dependent on its concentration and biological activity. This study aimed to improve the method of [...] Read more.

Albumin is a major prognostic factor for patients with advanced liver disease, dependent on its concentration and biological activity. This study aimed to improve the method of active albumin detection and elucidate its predictive validity of albumin activity across hepatic disease progression and etiology.

This study synthesized a novel ratiometric fluorescent probe with an improved structure of 2′-FBPBN. The technique was used to detect native human albumin (HA) activity in 244 patients with hepatitis B cirrhosis (LC) and 66 patients with hepatocellular carcinoma (HCC). Clinical and laboratory data were also collected.

Patients with LC and HCC were divided into normal albumin and low albumin (LA) groups. The median levels of albumin and HA activity in LC patients were 41.44 g/L and 51.85%, 28.51 g/L and 53.89%, respectively, while in HCC patients, they were 43.19 g/L and 33.69%, 30.77 g/L and 43.63%, respectively. The levels of total bilirubin, prothrombin time, international normalized ratio, native HA activity, Child-Pugh score, model for end-stage liver disease score, and model for end-stage liver disease-Na score were significantly higher in the LA groups, while the levels of platelet, cholesterol, and cholinesterase were lower compared to the normal albumin group (P < 0.05). The LA groups were more likely to suffer from hepatic encephalopathy and ascites. Patients with normal active HA had significantly higher survival rates than those with low active HA.

Native HA activity may outperform albumin as a prognostic indicator for assessing the severity of liver disease.

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231
Original Article Open Access
Mengxia Yang, Chunming Zhao, Tengfei Chen, Xiaolong Xu, Qingquan Liu
Published online August 30, 2024
Future Integrative Medicine. doi:10.14218/FIM.2024.00030
Abstract
Shufeng Jiedu Capsules (SFJD), a traditional Chinese medicine preparation, are widely used in the clinical treatment of influenza, yet their mechanism of action remains unclear. [...] Read more.

Shufeng Jiedu Capsules (SFJD), a traditional Chinese medicine preparation, are widely used in the clinical treatment of influenza, yet their mechanism of action remains unclear. This study aimed to systematically explore the molecular mechanism of SFJD in the treatment of influenza using network pharmacology and bioinformatics techniques.

The active ingredients of SFJD were retrieved from traditional Chinese medicine databases, and their targets were identified using the Swiss Target Prediction and TCMSP databases. Influenza disease genes were obtained from the GEO, GeneCards, and DisGeNET databases, and a Venn diagram was used to identify potential targets by mapping SFJD targets to influenza disease genes. Network construction and analysis of potential therapeutic targets were performed using the STRING12.0 database and Cytoscape3.9.1 software, leading to the identification of key targets. The expression of potential therapeutic targets in tissues and cells was retrieved using the BioGPS database. Functional enrichment analysis of these targets was conducted using the DAVID database. Molecular docking was then used to assess the interactions between key targets and core active ingredients.

SFJD contains 193 active ingredients and 985 targets. There are 510 influenza disease genes, 97 of which are potential therapeutic targets for SFJD in treating influenza, with 27 key targets identified through network construction and analysis. Tissue/cell-specific analysis revealed that 39 potential therapeutic targets are highly expressed in 37 specific tissues/cells. Functional enrichment analysis highlighted pathways such as the C-type lectin receptor signaling pathway, tumor necrosis factor signaling pathway, and hypoxia-inducible factor-1 signaling pathway. Molecular docking results indicated strong interactions between the core active ingredients and the key targets.

This study systematically reveals that the mechanism of action of SFJD in treating influenza is complex, involving multiple targets and pathways related to antiviral, anti-inflammatory, and immune regulation effects. The findings provide valuable reference information for future clinical treatment and basic research on influenza.

Full article
232
Original Article Open Access
Boyuan Ren, Jiayan Jin, Yichen Wang, Xiao Xu, Yun Liu, Hongfan Ding, Qiang Li, Ji-de Jin
Published online August 30, 2024
Future Integrative Medicine. doi:10.14218/FIM.2024.00031
Abstract
Radiation injury poses a serious threat to human health, causing complex and multifaceted damage to cells and tissues. Such injury can be caused by various factors, including nuclear [...] Read more.

Radiation injury poses a serious threat to human health, causing complex and multifaceted damage to cells and tissues. Such injury can be caused by various factors, including nuclear accidents, medical radiation therapy, and space travel. Currently, finding effective treatment methods and drugs to mitigate the harmful effects of radiation injury on the human body is a crucial research direction. This study aimed to explore the protective effects and mechanisms of Licochalcone B (Lico B) on radiation-induced cell damage and radiation-induced mortality in mice.

HaCaT cells, THP-1 cells, and HAEC cells were irradiated with a 10 Gray (Gy) dose of X-rays, while RAW 264.7 cells were irradiated with a 10 Gy dose of γ-rays. The cells were pre-treated with Lico B for 2 h before irradiation, and samples were collected 2 h after irradiation. Cell proliferation viability, oxidative stress levels, DNA damage, expression levels of inflammatory factors, matrix metalloproteinases, guanylate cyclase, and iron death-related factors were measured. C57BL/6 mice were exposed to total-body irradiation with a dose of 8 Gy or a combined dose of 6 Gy + 8 Gy of γ-rays to induce radiation injury. Lico B was injected intraperitoneally one day before irradiation and then administered for two consecutive days, with continuous observation for 20 days.

Mechanistically, Lico B significantly improved antioxidant levels, reduced DNA damage, and lowered the expression of inflammatory factors in HaCaT, THP-1, HAEC, and RAW 264.7 cells. Therapeutically, Lico B increased cell proliferation capacity and significantly extended the survival time of irradiated mice, demonstrating a strong radioprotective effect.

Lico B exhibits significant radioprotective effects and may serve as a potential radioprotective agent.

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233
Original Article Open Access
Andrés Tirado-Sánchez, Alexandro Bonifaz, Javier Araiza, Sofía Beutelspacher
Published online August 28, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2023.00060
Abstract
Nail psoriasis is common in patients with plaque psoriasis and is associated with morbidity, including onychomycosis, which can complicate psoriasis treatments and be difficult [...] Read more.

Nail psoriasis is common in patients with plaque psoriasis and is associated with morbidity, including onychomycosis, which can complicate psoriasis treatments and be difficult to differentiate. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is a fast and simple technique for identifying microorganisms through protein analysis. This study aimed to determine the sensitivity and specificity of MALDI-TOF for diagnosing onychomycosis in patients with nail psoriasis, by using conventional mycological and histological methods as the reference standard.

A prospective study was conducted on 88 patients with clinically and histopathologically confirmed nail psoriasis. One hundred nail samples were obtained for direct examination, fungal culture, and mass spectrometry. None of the patients were receiving antifungal or systemic immunosuppressive therapy at the time of sampling.

Potassium hydroxide preparation and fungal culture were positive in 58 out of 100 nail samples from patients with psoriasis. MALDI-TOF identified onychomycosis in 68 out of 100 samples, distinguishing these cases from nail psoriasis without onychomycosis (32 out of 100). An excellent correlation (0.95) was found between MALDI-TOF and conventional onychomycosis diagnostic methods. The sensitivity and specificity of MALDI-TOF for diagnosing onychomycosis in patients with psoriatic nails were 95.4% and 97.5%, respectively.

MALDI-TOF can be used to accurately differentiate cases of nail psoriasis without infection from those with onychomycosis.

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234
Original Article Open Access
Yuxin Chen, Tianqing Huang, Fei Li, Ehu Liu
Published online August 23, 2024
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00012
Abstract
Isofraxidin, an important coumarin compound found in the medicinal plant Sarcandra glabra, is reported to have anti-inflammatory activity. However, its natural concentration is [...] Read more.

Isofraxidin, an important coumarin compound found in the medicinal plant Sarcandra glabra, is reported to have anti-inflammatory activity. However, its natural concentration is insufficient to meet the existing demand for this valuable molecule. Therefore, biotechnological approaches are necessary to enhance the isofraxidin content.

Endophytes were isolated from the roots, stems, and leaves of Sarcandra glabra and fermented with Sarcandra glabra, respectively. The target strains capable of increasing isofraxidin content were screened using high-performance liquid chromatography. Their genes were amplified, and the polymerase chain reaction products were sequenced. BLAST analysis was used to compare the sequences with those in GenBank, and a phylogenetic tree was constructed for species identification.

Fifteen endophytic bacteria and six endophytic fungi were isolated from the roots, stems, and leaves of Sarcandra glabra. Among them, Enterobacter, Bacillus wiedmannii, Trametes versicolor from the roots, and Diaporthe celeris and Diaporthe hongkongensis from the leaves increased the isofraxidin content in Sarcandra glabra. The isofraxidin content in Sarcandra glabra fermented by endophytes Enterobacter, Bacillus wiedmannii, Trametes versicolor, Diaporthe celeris, and Diaporthe hongkongensis was 1.37, 1.27, 1.11, 1.40, and 1.16 times higher than in the blank samples, respectively.

The fermentation of Sarcandra glabra with specific endophytes can increase its isofraxidin content. These findings provide preliminary scientific evidence for the potential of using microorganisms to enhance the quality of traditional Chinese medicine.

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235
Letter to the Editor Open Access
Yizhao Ma, Zhenting Zhao, Bin Lan, Xiaohui Du, Pengyue Zhao
Published online August 22, 2024
Oncology Advances. doi:10.14218/OnA.2024.00018
236
Letter to the Editor Open Access
Shuai Ren, Lina Song, Marcus J. Daniels, Ying Tian, Zhongqiu Wang
Published online August 22, 2024
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2024.00016
237
Short Communication Open Access
Majed Saeed Nassar, Sayed Wajid, Nawal Alkatheeri, Ibrahim A. Wasfi
Published online August 20, 2024
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2023.00013S
Abstract
Camels are commonly administered butylscopolamine (BSA), an antimuscarinic quaternary ammonium derivative, to reduce spasms in the smooth muscles of their urinary and gastrointestinal [...] Read more.

Camels are commonly administered butylscopolamine (BSA), an antimuscarinic quaternary ammonium derivative, to reduce spasms in the smooth muscles of their urinary and gastrointestinal tracts. However, its presence in body fluids after racing is prohibited by animal racing authorities. The current study aimed to conduct a pilot pharmacokinetic study of BSA in healthy camels. The goal was to obtain initial pharmacokinetic parameters and use these parameters to predict plasma concentrations from the dose and clearance. This will help advise on a withdrawal time for BSA administration before camel racing. The pharmacokinetics of BSA were evaluated in three healthy camels after a single intravenous dose of 0.2 mg/kg body weight. Sensitive liquid chromatography with tandem mass spectrometry was used for the quantification of BSA and the internal standard, ipratropium, in plasma. BSA concentration versus time data were best described by a two-compartment open model. The pharmacokinetic parameters (median and range) were as follows: terminal elimination half-life was 2.29 (1.48–2.46) h, plasma clearance was 1,018.5 (772.4–1,024.0) mL/h/kg, volume of distribution at steady state was 931.9 (700.0–1,068.7) mL/kg, Cmax was 443.9 (351.1–443.9) ng/mL, and Tmax was 0.5 (0.25–0.75) h. BSA’s irrelevant plasma concentration was estimated to be 20 ng/mL. Consequently, it can be concluded that plasma would not contain BSA at the screening level of 20 ng/mL at the usual dose of 0.2 mg/kg body weight 24 h before camel racing.

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238
Letter to the Editor Open Access
Taha Yazal, Chia-Yang Li
Published online August 13, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00220
239
Letter to the Editor Open Access
James K.H. Ho, Prem H. Thurairajah, Daniel Q. Huang, Kristie H. Fan
Published online August 7, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00216
240
Original Article Open Access
Zi-Yuan Zou, Tian-Yi Ren, Jia-Qi Li, Ting-Ying Jiao, Meng-Yu Wang, Lei-Jie Huang, Shuang-Zhe Lin, Yuan-Yang Wang, Xiao-Zhen Guo, Ye-Yu Song, Rui-Xu Yang, Cen Xie, Jian-Gao Fan
Published online August 2, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00111
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more advanced form, metabolic dysfunction-associated steatohepatitis, have emerged as the most prevalent [...] Read more.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more advanced form, metabolic dysfunction-associated steatohepatitis, have emerged as the most prevalent liver diseases worldwide. Currently, lifestyle modification is the foremost guideline-recommended management strategy for MASLD. However, it remains unclear which detrimental signals persist in MASLD even after disease remission. Thus, we aimed to examine the persistent changes in liver transcriptomic profiles following this reversal.

Male C57BL/6J mice were divided into three groups: Western diet (WD) feeding, chow diet (CD) feeding, or diet reversal from WD to CD. After 16 weeks of feeding, RNA sequencing was performed on the mice’s livers to identify persistent alterations characteristic of MASLD. Additionally, RNA sequencing databases containing high-fat diet-fed P53-knockout mice and human MASLD samples were utilized.

WD-induced MASLD triggered persistent activation of the DNA damage response (DDR) and its primary transcription factor, P53, long after the resolution of the hepatic phenotype through dietary reversal. Elevated levels of P53 might promote apoptosis, thereby exacerbating metabolic dysfunction-associated steatohepatitis, as they strongly correlated with hepatocyte ballooning, an indicator of apoptosis activation. Moreover, P53 knockout in mice led to downregulated expression of apoptosis signaling in the liver. Mechanistically, P53 may regulate apoptosis by transcriptionally activating the expression of apoptosis-enhancing nuclease (AEN). Consistently, P53, AEN, and the apoptosis process all exhibited persistently elevated expression and showed a strong inter-correlation in the liver following dietary reversal.

The liver demonstrated upregulation of DDR signaling and the P53-AEN-apoptosis axis both during and after exposure to WD. Our findings provide new insights into the mechanisms of MASLD relapse, highlighting DDR signaling as a promising target to prevent MASLD recurrence.

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