Exploring the potential of omics technologies in medicinal plant research: a review in Colombia / Explorando el potencial de las tecnologías ómicas en la investigación de plantas medicinales: una revisión en Colombia

This review presents advances in the implementation of high - throughput se quencing and its application to the knowledge of medicinal plants. We conducted a bibliographic search of papers published in PubMed, Science Direct, Google Scholar, Scopus, and Web of Science databases and analyzed the obtained data using VOSviewer (versi on 1.6.19). Given that medicinal plants are a source of specialized metabolites with immense therapeutic values and important pharmacological properties, plant researchers around the world have turned their attention toward them and have begun to examine t hem widely. Recent advances in sequencing technologies have reduced cost and time demands and accelerated medicinal plant research. Such research leverages full genome sequencing, as well as RNA (ribonucleic acid) sequencing and the analysis of the transcr iptome, to identify molecular markers of species and functional genes that control key biological traits, as well as to understand the biosynthetic pathways of bioactive metabolites and regulatory mechanisms of environmental responses. As such, the omics ( e.g., transcriptomics, metabolomics, proteomics, and genomics, among others) have been widely applied within the study of medicinal plants, although their usage in Colombia is still few and, in some areas, scarce. (185)

El extracto de cloroformo (CE) y las fracciones obtenidas de las raíces de Aldama arenaria se evaluaron para determinar su actividad antiproliferativa in vitro contra 10 líneas ce lulares tumorales humanas [leucemia (K - 562), mama (MCF - 7), ovario que expresa un fenotipo resistente a múltiples fármacos (NCI/ADR - RES), melanoma (UACC - 62), pulmón (NCI - H460), próstata (PC - 3), colon (HT29), ovario (OVCAR - 3), glioma (U251) y riñón (786 - 0)]. CE presentó actividad antiproliferativa débil a moderada (log GI 50 medio 1.07), mientras que las fracciones 3 y 4, enriquecidas con diterpenos de tipo pimarane [ent - pimara - 8 (14), ácido 15 - dien - 19 - oico y ent - 8(14),15 - pimaradien - 3 ß - ol], presentaron activid ad moderada a potente para la mayoría de las líneas celulares, con un log GI 50 medio de 0.62 y 0.59, respectivamente. Los resultados mostraron una acción antiproliferativa in vitro prometedora de las muestras obtenidas de A. arenaria , con los mejores resul tados para NCI/ADR - RES, HT29 y OVCAR - 3, y valores de TGI que van desde 5.95 a 28.71 µg.mL - 1, demostrando que los compuestos de esta clase pueden ser prototipos potenciales para el descubrimiento de nuevos agentes terapéuticos

Ethnobotanical knowledge on non-conventional food plants and medicinal plants in Extractivist Reserve in the Brazilian Amazon / Conocimiento etnobotánico sobre plantas alimenticias no convencionales y plantas medicinales en una Reserva Extractivista en la Amazonía Brasileña

Information on the knowledge and ways of using food and medicinal plants by traditional populations, family farmers and Brazilian native population in the Amazon is essential to guarantee the food sovereignty of these groups. This study was conducted using semi-structured interviews applied to local respondents. A total of 269 species of both non-conventional food plants and medicinal plants were identified, distributed in 83 botanical families and 198 genera. The Arecaceae and Lamiaceae families had the highest species richness (11 and 7, respectively). The Shannon-Wiener (H') and Pielou (J') diversity indices were considered high (5.02 and 0.9, respectively) when compared to other ethnobotanical works. In the environment in which these families are found, these species become the only food and medicinal resources available.

La información sobre los saberes y formas de uso de las plantas alimenticias y medicinales por parte de las poblaciones tradicionales, agricultores familiares e indígenas brasileños en la Amazonía es fundamental para garantizar la soberanía alimentaria de estos grupos. Este estudio se realizó utilizando entrevistas semiestructuradas aplicadas a encuestados locales. Se identificaron un total de 269 especies tanto de plantas alimenticiasno convencionales como de plantas medicinales, distribuidas en 83 familias botánicas y 198 géneros. Las familias Arecaceae y Lamiaceae tuvieron la mayor riqueza de especies (11 y 7, respectivamente). Los índices de diversidad de Shannon-Wiener (H') y Pielou (J') fueron considerados altos (5,02 y 0,9, respectivamente) en comparación con otros trabajos etnobotánicos. En el ambiente en que se encuentran estas familias, estas especies se convierten en los únicos recursos alimenticios y medicinales disponibles.

Evidence-based interventions for identifying candidate quality indicators to assess quality of care in diabetic foot clinics: a scoping review.

BACKGROUND: Foot ulcers in people with diabetes are a serious complication requiring a complex management and have a high societal impact. Quality monitoring systems to optimize diabetic foot care exist, but a formal and more evidence-based approach to develop quality indicators (QIs) is lacking. We aimed to identify a set of candidate indicators for diabetic foot care by adopting an evidence-based methodology. METHODS: A systematic search was conducted across four academic databases: PubMed, Embase CINAHL and Cochrane Library. Studies that reported evidence-based interventions related to organization or delivery of diabetic foot care were searched. Data from the eligible studies were summarized and used to formulate process and structure indicators. The evidence for each candidate QI was described in a methodical and transparent manner. The review process was reported according to the "Preferred Reported Items for Systematic reviews and Meta-Analysis" (PRISMA) statements and its extension for scoping reviews. RESULTS: In total, 981 full-text articles were screened, and 322 clinical studies were used to formulate 42 candidate QIs. CONCLUSIONS: An evidence-based approach could be used to select candidate indicators for diabetic foot ulcer care, relating to the following domains: wound healing interventions, peripheral artery disease, offloading, secondary prevention, and interventions related to organization of care. In a further step, the feasibility of the identified set of indicators will be assessed by a multidisciplinary panel of diabetic foot care stakeholders.

Organ Neuroprosthetics: Connecting Transplanted and Artificial Organs with the Nervous System.

Implantable neural interfaces with the central and peripheral nervous systems are currently used to restore sensory, motor, and cognitive functions in disabled people with very promising results. They have also been used to modulate autonomic activities to treat diseases such as diabetes or hypertension. Here, this study proposes to extend the use of these technologies to (re-)establish the connection between new (transplanted or artificial) organs and the nervous system in order to increase the long-term efficacy and the effective biointegration of these solutions. In this perspective paper, some clinically relevant applications of this approach are briefly described. Then, the choices that neural engineers must implement about the type, implantation location, and closed-loop control algorithms to successfully realize this approach are highlighted. It is believed that these new "organ neuroprostheses" are going to become more and more valuable and very effective solutions in the years to come.

Temporal trends and regional variability in BRAF and KRAS genetic testing in Denmark (2010-2022): Implications for precision medicine.

OBJECTIVE: This study aims to evaluate the developments in the testing of Kirsten Rat Sarcoma viral oncogene homolog (KRAS) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations across different cancer types and regions in Denmark from 2010 to 2022. STUDY DESIGN AND SETTING: Using comprehensive data from the Danish health registries, we linked molecular test results from the Danish Pathology Registry with cancer diagnoses from the Danish National Patient Registry between 2010 and 2022. We assessed the frequency and distribution of KRAS and BRAF mutations across all cancer types, years of testing, and the five Danish regions. RESULTS: The study included records of KRAS testing for 30 671 patients and BRAF testing for 30 860 patients. Most KRAS testing was performed in colorectal (78%) and lung cancer (18%), and BRAF testing in malignant melanoma (13%), colorectal cancer (67%), and lung cancer (12%). Testing rates and documentation mutational subtypes increased over time. Reporting of wildtype results varied between lung and colorectal cancer, with underreporting in lung cancer. Regional variations in testing and reporting were observed. CONCLUSION: Our study highlights substantial progress in KRAS and BRAF testing in Denmark from 2010 to 2022, evidenced by increased and more specific reporting of mutational test results, thereby improving the precision of cancer diagnosis and treatment. However, persistent regional variations and limited testing for cancer types beyond melanoma, colorectal, and lung cancer highlight the necessity for a nationwide assessment of the optimal testing approach.

Molecular Heterogeneity in Leiomyosarcoma and Implications for Personalised Medicine.

OPINION STATEMENT: Leiomyosarcoma (LMS) is one of the more common subtypes of soft tissue sarcomas (STS), accounting for about 20% of cases. Differences in anatomical location, risk of recurrence and histomorphological variants contribute to the substantial clinical heterogeneity in survival outcomes and therapy responses observed in patients. There is therefore a need to move away from the current one-size-fits-all treatment approach towards a personalised strategy tailored for individual patients. Over the past decade, tissue profiling studies have revealed key genomic features and an additional layer of molecular heterogeneity among patients, with potential utility for optimal risk stratification and biomarker-matched therapies. Furthermore, recent studies investigating intratumour heterogeneity and tumour evolution patterns in LMS suggest some key features that may need to be taken into consideration when designing treatment strategies and clinical trials. Moving forward, national and international collaborative efforts to aggregate expertise, data, resources and tools are needed to achieve a step change in improving patient survival outcomes in this disease of unmet need.

Behavior Change Approaches in Digital Technology-Based Physical Rehabilitation Interventions Following Stroke: Scoping Review.

BACKGROUND: Digital health technologies (DHTs) are increasingly used in physical stroke rehabilitation to support individuals in successfully engaging with the frequent, intensive, and lengthy activities required to optimize recovery. Despite this, little is known about behavior change within these interventions. OBJECTIVE: This scoping review aimed to identify if and how behavior change approaches (ie, theories, models, frameworks, and techniques to influence behavior) are incorporated within physical stroke rehabilitation interventions that include a DHT. METHODS: Databases (Embase, MEDLINE, PsycINFO, CINAHL, Cochrane Library, and AMED) were searched using keywords relating to behavior change, DHT, physical rehabilitation, and stroke. The results were independently screened by 2 reviewers. Sources were included if they reported a completed primary research study in which a behavior change approach could be identified within a physical stroke rehabilitation intervention that included a DHT. Data, including the study design, DHT used, and behavior change approaches, were charted. Specific behavior change techniques were coded to the behavior change technique taxonomy version 1 (BCTTv1). RESULTS: From a total of 1973 identified sources, 103 (5%) studies were included for data charting. The most common reason for exclusion at full-text screening was the absence of an explicit approach to behavior change (165/245, 67%). Almost half (45/103, 44%) of the included studies were described as pilot or feasibility studies. Virtual reality was the most frequently identified DHT type (58/103, 56%), and almost two-thirds (65/103, 63%) of studies focused on upper limb rehabilitation. Only a limited number of studies (18/103, 17%) included a theory, model, or framework for behavior change. The most frequently used BCTTv1 clusters were feedback and monitoring (88/103, 85%), reward and threat (56/103, 54%), goals and planning (33/103, 32%), and shaping knowledge (33/103, 32%). Relationships between feedback and monitoring and reward and threat were identified using a relationship map, with prominent use of both of these clusters in interventions that included virtual reality. CONCLUSIONS: Despite an assumption that DHTs can promote engagement in rehabilitation, this scoping review demonstrates that very few studies of physical stroke rehabilitation that include a DHT overtly used any form of behavior change approach. From those studies that did consider behavior change, most did not report a robust underpinning theory. Future development and research need to explicitly articulate how including DHTs within an intervention may support the behavior change required for optimal engagement in physical rehabilitation following stroke, as well as establish their effectiveness. This understanding is likely to support the realization of the transformative potential of DHTs in stroke rehabilitation.

[Personalized medicine in oncology]. / Personalisierte Medizin in der Onkologie.

Due to the considerable technological progress in molecular and genetic diagnostics as well as increasing insights into the molecular pathogenesis of diseases, there has been a fundamental paradigm shift in the past two decades from a "one-size-fits-all approach" to personalized, molecularly informed treatment strategies. Personalized medicine or precision medicine focuses on the genetic, physiological, molecular, and biochemical differences between individuals and considers their effects on the development, prevention, and treatment of diseases. As a pioneer of personalized medicine, the field of oncology is particularly noteworthy, where personalized diagnostics and treatment have led to lasting change in the treatment of cancer patients in recent years. In this article, the significant change towards personalized treatment concepts, especially in the field of personalized oncology, will be discussed and examined in more detail.

Quality by Design Considerations for Drop-on-Demand Point-of-Care Pharmaceutical Manufacturing of Precision Medicine.

Distributed and point-of-care (POC) manufacturing facilities enable an agile pharmaceutical production paradigm that can respond to localized needs, providing personalized and precision medicine. These capabilities are critical for narrow therapeutic index drugs and pediatric or geriatric dosing, among other specialized needs. Advanced additive manufacturing, three-dimensional (3D) printing, and drop-on-demand (DoD) dispensing technologies have begun to expand into pharmaceutical production. We employed a quality by design (QbD) approach to identify critical quality attributes (CQAs), critical material attributes (CMAs), and critical process parameters (CPPs) of a POC pharmaceutical manufacturing paradigm. This theoretical framework encompasses the production of active pharmaceutical ingredient (API) "inks" at a centralized facility, which are distributed to POC sites for DoD dispensing into/onto delivery vehicles (e.g., orodispersible films, capsules, single liquid dose vials). Focusing on the POC dispensing/dosing processes, QbD considerations and cause-and-effect analyses identified the dispensed API quantity and solid-state form (CQAs), as well as the nozzle diameter, system pressure channel, and number of drops dispensed (CPPs) for detailed investigation. Final assay quantification and content uniformity CQAs were measured from demonstrative levothyroxine sodium single-dose liquid vials of glycerin/water, meeting the standard acceptance values. Each POC facility is unlikely to maintain full quality control laboratory capabilities, requiring the development of appropriate atline or inline methods to ensure quality control. We developed control strategies, including atline ultraviolet-visible (UV-vis) verification of the API ink prior to dispensing, inline drop counting during dispensing, intermediate atline-dispensed volume checks, and offline batch confirmation by liquid chromatography-tandem mass spectrometry (LC-MS/MS) following production.

Differential relationships between physical activity and pain phenotypes in individuals with spinal cord injury.

BACKGROUND: Chronic pain affects 70% of individuals with spinal cord injury (SCI) and leads to declines in health and quality of life. Neuropathic and nociceptive pain are phenotypes derived from different mechanisms that contribute to pain perception. The objective of this research was to investigate differential pain responses to moderate-to-vigorous physical activity (MVPA) in two chronic pain phenotypes: neuropathic and nociceptive pain. METHODS: Community-based physical activity levels were collected for one week in 17 individuals with SCI using a wrist-worn accelerometer, and daily pain ratings were assessed and categorized by phenotype. Physical activity levels were summarized to calculate minutes of MVPA. Correlational analyses were conducted to compare relationships between pain intensity and MVPA across individual participants and between pain phenotype groups. RESULTS: The neuropathic pain group revealed significant negative correlation between MVPA and pain intensity. In the nociceptive pain group, there was no significant correlation between MVPA and pain intensity. Further analysis revealed two subgroups of positive (N = 4) and negative (N = 3) correlations between MVPA and pain intensity. Pain location differed between the subgroups of nociceptive pain. Individuals with negative correlation experienced neck and upper back pain, whereas individuals with positive correlation experienced unilateral upper extremity pain. CONCLUSION: Differential relationships exist between pain phenotypes and MVPA in individuals with SCI. Pain location differed between the subgroups of nociceptive pain, which we presume may indicate the presence of nociplastic pain in some individuals. These results may contribute to the advancement of personalized pain management by targeting non-pharmacological interventions for specific pain phenotypes.Trial registration: ClinicalTrials.gov identifier: NCT05236933..

Neurological outcome of cardiac arrest patients in mountain areas: An analysis of the Northern French Alps Emergency Network.

BACKGROUND: Mountainous areas pose a challenge for the out-of-hospital cardiac arrest (OHCA) chain of survival. Survival rates for OHCAs in mountainous areas may differ depending on the location. Increased survival has been observed compared to standard location when OHCA occurred on ski slopes. Limited data is available about OHCA in other mountainous areas. The objective was to compare the survival rates with a good neurological outcome of OHCAs occurring on ski slopes (On-S) and off the ski slopes (OffS) compared to other locations (OL). METHODS: Analysis of prospectively collected data from the cardiac arrest registry of the Northern French Alps Emergency Network (RENAU) from 2015 to 2021. The RENAU corresponding to an Emergency Medicine Network between all Emergency Medical Services and hospitals of 3 counties (Isère, Savoie, Haute-Savoie). The primary outcome was survival at 30 days with a Cerebral Performance Category scale (CPC) of 1 or 2 (1: Good Cerebral Performance, 2: Moderate Cerebral Disability). RESULTS: A total of 9589 OHCAs were included: 213 in the On-S group, 141 in the Off-S group, and 9235 in the OL group. Cardiac etiology was more common in On-S conditions (On-S: 68.9% vs OffS: 51.1% vs OL: 66.7%, p < 0.001), while Off-S cardiac arrests were more often due to traumatic circumstances (OffS: 39.7% vs On-S: 21.7% vs OL: 7.7%, p < 0.001). Automated external defibrillator (AED) use before rescuers' arrival was lower in the Off-S group than in the other two groups (On-S: 15.2% vs OL: 4.5% vs OffS: 3.7%; p < 0.002). The first AED shock was longer in the Off-S group (median time in minutes: OffS: 22.0 (9.5-35.5) vs On-S: 10.0 (3.0-19.5) vs OL: 16.0 (11.0-27.0), p = 0.03). In multivariate analysis, on-slope OHCA remained a positive factor for 30-day survival with a CPC score of 1 or 2 with a 1.96 adjusted odds ratio (95% confidence interval (CI), 1.02-3.75, p = 0.04), whereas off-slope OHCA had an 0.88 adjusted odds ratio (95% CI, 0.28-2.72, p = 0.82). CONCLUSIONS: OHCAs in ski-slopes conditions were associated with an improvement in neurological outcomes at 30 days, whereas off-slopes OHCAs were not. Ski-slopes rescue patrols are efficient in improving outcomes.

How artificial intelligence could transform emergency care.

Artificial intelligence (AI) in healthcare is the ability of a computer to perform tasks typically associated with clinical care (e.g. medical decision-making and documentation). AI will soon be integrated into an increasing number of healthcare applications, including elements of emergency department (ED) care. Here, we describe the basics of AI, various categories of its functions (including machine learning and natural language processing) and review emerging and potential future use-cases for emergency care. For example, AI-assisted symptom checkers could help direct patients to the appropriate setting, models could assist in assigning triage levels, and ambient AI systems could document clinical encounters. AI could also help provide focused summaries of charts, summarize encounters for hand-offs, and create discharge instructions with an appropriate language and reading level. Additional use cases include medical decision making for decision rules, real-time models that predict clinical deterioration or sepsis, and efficient extraction of unstructured data for coding, billing, research, and quality initiatives. We discuss the potential transformative benefits of AI, as well as the concerns regarding its use (e.g. privacy, data accuracy, and the potential for changing the doctor-patient relationship).

Fabrication of amino- and hydroxyl dual-functionalized magnetic microporous organic network for extraction of zearalenone from traditional Chinese medicine prior to the HPLC determination.

Efficient enrichment of trace zearalenone (ZEN) from the complex traditional Chinese medicine (TCM) samples is quite difficult, but of great significance for TCM quality control. Herein, we reported a novel magnetic solid phase extraction (MSPE) strategy for ZEN enrichment using the amino- and hydroxyl dual-functionalized magnetic microporous organic network (Fe3O4@MON-NH2-OH) as an advanced adsorbent combined with the high-performance liquid chromatography (HPLC) determination. Efficient extraction of ZEN was achieved via the possible hydrogen bonding, hydrophobic, and π-π interactions between Fe3O4@MON-NH2-OH and ZEN. The adsorption capacity of Fe3O4@MON-NH2-OH for ZEN was 215.0 mg g-1 at the room temperature, which was much higher than most of the reported adsorbents. Under the optimal condition, the developed Fe3O4@MON-NH2-OH-MSPE-HPLC method exhibited wide linear range (5-2500 µg L-1), low limits of detection (1.4-35 µg L-1), less adsorbent consumption (5 mg), and large enhancement factor (95) for ZEN. The proposed method was successfully applied to detect trace ZEN from 10 kinds of real TCM samples. Conclusively, this work demonstrates the Fe3O4@MON-NH2-OH can effectively extract trace ZEN from the complex TCM matrices, which may open up a new way for the application of MONs in the enrichment and extraction of trace contaminants or active constituents from the complex TCM samples.

Precision medicine in colorectal cancer: Leveraging multi-omics, spatial omics, and artificial intelligence.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths. Recent advancements in genomic technologies and analytical approaches have revolutionized CRC research, enabling precision medicine. This review highlights the integration of multi-omics, spatial omics, and artificial intelligence (AI) in advancing precision medicine for CRC. Multi-omics approaches have uncovered molecular mechanisms driving CRC progression, while spatial omics have provided insights into the spatial heterogeneity of gene expression in CRC tissues. AI techniques have been utilized to analyze complex datasets, identify new treatment targets, and enhance diagnosis and prognosis. Despite the tumor's heterogeneity and genetic and epigenetic complexity, the fusion of multi-omics, spatial omics, and AI shows the potential to overcome these challenges and advance precision medicine in CRC. The future lies in integrating these technologies to provide deeper insights and enable personalized therapies for CRC patients.

The application of umbilical cord blood-derived platelet gel for skin ulcers associated with chronic graft-versus-host disease in pediatrics: A randomized trial.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative strategy against a variety of malignant and nonmalignant disorders. However, acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) commonly complicate this approach, culminating in substantial morbidities and mortalities. The integumentary system is the preponderant organ involved in cGVHD, and its response to existing treatments, including well-versed immunosuppressants and novel targeted therapies, is not desirable. Despite the rarity, ulcers of sclerotic skin cGVHD are treatment-refractory and associated with significant morbidities and an exaggerated risk of infectious complications. Platelet-rich plasma (PRP) and its derivatives are endowed with growth factors and proangiogenic molecules and hold regenerative potential. OBJECTIVES: To assess the safety and efficacy of the application of platelet gel-containing dressing for the management of ulcerative skin cGVHD in pediatric patients. STUDY DESIGN: This randomized trial is conducted at the hematopoietic stem cell transplantation unit of the Children's Medical Center Hospital in Tehran, Iran. Twenty-one pediatric patients (aged between 5 and 15 years) were initially enrolled, and 16 met the inclusion criteria. All cases (four females) were recipients of allo-HSCT who had been complicated with symmetrically or near-symmetrically ulcerative sclerotic skin cGVHD. Fresh umbilical cord blood (UCB) was obtained from healthy donors and underwent centrifugation using a novel PRP preparation kit in a single-step process. Platelet gel was produced by adding thrombin to the isolated buffy coat layer. Two similar ulcers of each patient were randomized to receive either conventional dressing or platelet gels up to 6 times. At each time point evaluation, ulcer size and its relative reduction compared to the basal size were recorded. RESULTS: Included patients received a total of 80 platelet gel-containing dressings. While the mean sizes of randomized ulcers at the beginning of the study were similar, their differences became significant 15 days after the initiation of intervention (P = 0.019). In addition, the mean reduction in the ulcers' surface area (in comparison to their baseline values) was significantly higher for the intervention arm at all evaluation points (P = 0.001 for day five and P < 0.001 for subsequent time points). At the end of the trial, the number of ulcers with a more than 50% reduction in size was 14 (87.5%) in the intervention arm (including six completely healed ulcers) versus one (6.25%, which was not completely healed) in the control arm (P < 0.001). None of the patients exhibited any localized or systemic treatment-related adverse events. CONCLUSIONS: In this study, using a relatively large number of cases, we showed that UCB-derived platelet gel is a safe, feasible, and effective curative approach for skin ulcers of sclerotic skin cGVHD in pediatric patients. Designing upcoming trials on the efficacy of this therapeutic approach for ocular, mucosal, and acute skin GVHD is prudent. TRIAL REGISTRATION: Retrospectively registered at the Iranian Registry of Clinical Trials (registration number IRCT20190101042197N1) on August 24, 2020.

A Comprehensive Review of Bupleuri Radix and its Bioactive Components： with a Major Focus on Treating Chronic Liver Diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleuri Radix (BR) has been recognized as an essential herbal medicine for relieving liver depression for thousands of years. Contemporary research has provided compelling evidence of its pharmacological effects, including anti-inflammatory, immunomodulatory, metabolic regulation, and anticancer properties, positioning it as a promising treatment option for various liver diseases. Hepatitis, steatohepatitis, cirrhosis, and liver cancer are among the prevalent and impactful liver diseases worldwide. However, there remains a lack of comprehensive systematic reviews that explore the prescription, bio-active components, and underlying mechanisms of BR in treating liver diseases. AIM OF THE REVIEW: To summarize the BR classical Chinese medical prescription and ingredients in treating liver diseases and their mechanisms to inform reference for further development and research. MATERIALS AND METHODS: Literature in the last three decades of BR and its classical Chinese medical prescription and ingredients were collated and summarized by searching PubMed, Wiley, Springer, Google Scholar, Web of Science, CNKI, etc. RESULTS: BR and its classical prescriptions, such as Xiao Chai Hu decoction, Da Chai Hu decoction, Si Ni San, and Chai Hu Shu Gan San, have been utilized for centuries as effective therapies for liver diseases, including hepatitis, steatohepatitis, cirrhosis, and liver cancer. BR is a rich source of active ingredients, such as saikosaponins, polysaccharides, flavonoids, sterols, organic acids, and so on. These bioactive compounds exhibit a wide range of beneficial effects, including anti-inflammatory, antioxidant, immunomodulatory, and lipid metabolism regulation. However, it is important to acknowledge that BR and its constituents can also possess hepatotoxicity, which is associated with cytochrome P450 (CYP450) enzymes and oxidative stress. Therefore, caution should be exercised when using BR in therapeutic applications to ensure the safe and appropriate utilization of its potential benefits while minimizing any potential risks. CONCLUSIONS: To sum up, BR, its compounds, and its based traditional Chinese medicine are effective in liver diseases through multiple targets, multiple pathways, and multiple effects. Advances in pharmacological and toxicological investigations of BR and its bio-active components in the future will provide further contributions to the discovery of novel therapeutics for liver diseases.

Mitochondrial calcium uniporter as biomarker and therapeutic target for breast cancer: Prognostication, immune microenvironment, epigenetic regulation and precision medicine.

INTRODUCTION: Mitochondrial calcium uniporter (MCU) is a central subunit of MCU complex that regulate the levels of calcium ions within mitochondria. A comprehensive understanding the implications of MCU in clinical prognostication, biological understandings and therapeutic opportunity of breast cancer (BC) is yet to be determined. OBJECTIVES: This study aims to investigate the role of MCU in predictive performance, tumor progression, epigenetic regulation, shaping of tumor immune microenvironment, and pharmacogenetics and the development of anti-tumor therapy for BC. METHODS: The downloaded TCGA datasets were used to identify predictive ability of MCU expressions via supervised learning principle. Functional enrichment, mutation landscape, immunological profile, drug sensitivity were examined using bioinformatics analysis and confirmed by experiments exploiting human specimens, in vitro and in vivo models. RESULTS: MCU copy numbers increase with MCU gene expression. MCU expression, but not MCU genetic alterations, had a positive correlation with known BC prognostic markers. Higher MCU levels in BC showed modest efficacy in predicting overall survival. In addition, high MCU expression was associated with known BC prognostic markers and with malignancy. In BC tumor and sgRNA-treated cell lines, enrichment pathways identified the involvement of cell cycle and immunity. miR-29a was recognized as a negative epigenetic regulator of MCU. High MCU levels were associated with increased mutation levels in oncogene TP53 and tumor suppression gene CDH1, as well as with an immunosuppressive microenvironment. Sigle-cell sequencing indicated that MCU mostly mapped on to tumor cell and CD8 T-cells. Inter-databases verification further confirmed the aforementioned observation. miR-29a-mediated knockdown of MCU resulted in tumor suppression and mitochondrial dysfunction, as well as diminished metastasis. Furthermore, MCU present pharmacogenetic significance in cellular docetaxel sensitivity and in prediction of patients' response to chemotherapeutic regimen. CONCLUSION: MCU shows significant implication in prognosis, outcome prediction, microenvironmental shaping and precision medicine for BC. miR-29a-mediated MCU inhibition exerts therapeutic effect in tumor growth and metastasis.

Management of oral manifestations of a child with Heimler Syndrome-2.

Heimler Syndrome 2 (HS-2) is a rare, autosomal recessive mild form of a peroxisomal biogenesis disorder. Though knowledge regarding the disorder is limited, emerging research has found that sensorineural hearing loss, occasional or late onset pigmentation, amelogenesis imperfecta and nail abnormalities are clinical characteristics representative of HS-2.A school-aged male presented to the dental department with a chief complaint of a lack of enamel on multiple teeth. The patient's medical history was significant for patent ductus arteriosus, bilateral sensorineural hearing loss and biallelic mutation of the PEX6 gene. The clinical exam revealed dental crowding, hypoplasia, hypo-calcification of multiple teeth and enlarged pulp chambers of maxillary molars. This case report details the clinical findings associated with HS-2, the comprehensive dental treatment to be rendered to the patient, and critical information to paediatric dentists and general dentists so that they can make proper referrals to medical specialties.