Genomic medicine and cancer clinical trial in Thailand

Introduction Cancer treatment has been revolutionized with the advent of targeted therapy and immunotherapy.In the past,when cancer treatment modalities were restricted,conventional chemotherapy was the only option for systemic disease.Because chemotherapy empirically affects all dividing cells,the targets are virtually non-specific.In this regard,toxic effects on normal tissue are essentially inevitable.

Progress of mitochondrial and endoplasmic reticulum-associated signaling and its regulation of chronic liver disease by Chinese medicine

The endoplasmic reticulum(ER)is connected to mitochondria through mitochondria-associated ER membranes(MAMs).MAMs provide a framework for crosstalk between the ER and mitochondria,playing a crucial role in regulating cellular calcium balance,lipid metabolism,and cell death.Dysregulation of MAMs is involved in the development of chronic liver disease(CLD).In CLD,changes in MAMs structure and function occur due to factors such as cellular stress,inflammation,and oxidative stress,leading to abnormal interactions between mitochondria and the ER,resulting in liver cell injury,fibrosis,and impaired liver function.Traditional Chinese medicine has shown some research progress in regulating MAMs signaling and treating CLD.This paper reviews the literature on the association between mitochondria and the ER,as well as the intervention of traditional Chinese medicine in regulating CLD.

Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

Visualizing traumatic brain injury:ocular clues for diagnosis and assessment

Traumatic brain injury (TBI) is defined as damage to the brain resulting from an external sudden physical force or shock to the head.It is considered a silent public health epidemic causing significant death and disability globally.There were 64,000 TBI related deaths reported in the USA in 2020,with about US$76 billion in direct and indirect medical costs annually.

Targeting key signalling pathways in oesophageal adenocarcinoma:A reality for personalised medicine?

Cancer treatments are rapidly changing.Curative treatment for oesophageal adenocarcinoma currently involves surgery and cytotoxic chemotherapy or chemoradiotherapy.Outcomes for both regimes are generally poor as a result of tumor recurrence.We have reviewed the key signalling pathways associated with oesophageal adenocarcinomas and discussed the recent trials of novel agents that attempt to target these pathways.There are many trials underway with the aim of improving survival in oesophageal cancer.Currently,phase 2 and 3 trials are focused on MAP kinase inhibition,either through inhibition of growth factor receptors or signal transducer proteins.In order to avoid tumor resistance,it appears to be clear that targeted therapy will be needed to combat the multiple signalling pathways that are in operation in oesophageal adenocarcinomas.This may be achievable in the future with the advent of gene signatures and a combinatorial approach.

Biomarker-guided drug therapy: personalized medicine for treating Alzheimer’s disease

Alzheimer’s disease(AD)is a progressive neurodegenerative disorder associated with significant memory decline and cognitive impairment.AD is characterized by two classical neuropathological hal lmarks,namely the amyloid-beta(Aβ)plaques and neurofibril tangles.Currently,there are no disease-modifying treatments available for AD,except for a couple of the US Food and Drug Administration(FDA)-approved drugs to improve cognitive function by blocking N-methyl-D-aspartate receptors or cholinesterase activity(Panza et al.,2019).

OBSERVATION ON THE EFFECTS OF CHINESE MEDICINE ZHENXUANYIN FOR IMPROVING CEREBRAL BLOOD FLOW IN RATS WITH CEREBRAL ISCHEMIA

Zhenxuanyin (镇眩饮) is composed of pure Chinese medicinal herbs, such as gastrodia tuber, poria cocos, ligusticum wallichii etc. 4-verssel occlusion (4VO) model rats were reperfused after 30 minutes’ complete occlusion, and Zhenxuanyin was administered 3 times a day. 24 hours later, 123I-IMP uptake in the brain was evaluated as an index of cerebral blood flow (CBF). The results show that Zhenxuanyin (0.03g kg, 0.3g kg, Ig kg, or 3g/ kg a day) can greatly improve the blood flow in the main cerebral regions, and 0.3g/ kg can increase cerebral blood flow (CBF) to the normal level.

Overview of Research Trends in Precious Chinese Medicines

Introduction Traditional Chinese medicine(TCM)has continued through centuries to this day since the ancient times and has contributed greatly to the well-being maintenance and disease treatment in China.[1-3]Before the ushering in of Western medicine into China in the 19th century,TCM had been the major healthcare and medical modality in Chinese communities.[4]This ancient art of healing has not diminished over time;conversely,it is now widely accepted by patients both in China and around the world owing to the shift of the disease spectrum and the rise of the“return to nature”paradigm.Moreover,TCM is attracting increasing attention from research circle worldwide.[5]At present,TCM is used in approximately 45%of the world’s countries,and a large amount of Chinese medicine raw materials is exported from China,and some of these Chinese medicines are collected directly from the wild.[6,7]Owing to the popularity of Chinese medicine around the world,the natural resources required for Chinese medicine production can hardly meet the rapidly increasing demand.Wild herbal resources are decreasing by approximately 30%every year.[5,8,9].

Availability, Prices and Affordability of Glaucoma Medicines among Private Pharmacies of Nampula City in Mozambique

Introduction: Glaucoma is a group of chronically progressive disorders of the optic nerve and a worldwide leading cause of irreversible vision loss. Eye chronic diseases including glaucoma are major public health problems around the world, rapidly increasing with a growing and aging population. The treatment of chronic diseases lasts a lifetime. The purpose of this study is to assess the availability, prices and affordability of the medicines for glaucoma management in private pharmacies of Nampula City in Mozambique. Material and Methods: The standardized methodology designed by the World Health Organization and Health Action International was employed to conduct the study about the availability, price and affordability of glaucoma medicines in Nampula City from October to November 2021. Data were collected in 39 private pharmacies using a survey with fifteen glaucoma Medicines. Results: The Average of medicines availability was 46.6% (0.0% - 71.8%) with a mean of 8.86. The availability level demonstrated that 14 (93.3%) of all surveyed glaucoma medicines were very low and 1 (6.67%) was fairly high. Timolol was the most available medicine, found in 28 (71.8%) while apraclonidine, carteolol, levobunolol, carbachol, brinzolamide, bimatoprost, travoprost and unoprostone were not available. The medicine with the lowest price was latanoprost (2.84 USD) and the higher was acetazolamide (23.58 USD). None of the surveyed medicines were considered affordable. Conclusion: The majority of surveyed glaucoma medicines were not available and they were totally unaffordable against the defined thresholds. Policy strategy and technical options should be driven and implemented by the government to ensure the availability and affordability of glaucoma medicines at various levels of the Mozambican healthcare system.

Surrogacy in Reproductive Medicine: Ethical and Legal Analysis of the Procedure

This text sets out the different arguments regarding surrogacy as a reproductive medicine tech-nique in Colombia. The procedure is described, as well as the legal matters that this issue generates. Gestational carriers appear as an alternative for couples who want to have a child but they are not able to conceive because of infertility issues and do not want to go through an adoption process. Therefore, they adhere to surrogacy as an alternative of assisted human reproduction;a procedure that in Colombia faces serious legal gaps and causes ethical dilemmas in the collective imagery. These situations suggest an open discussion through a dialectics between the scientific progress advances, the lack of legal regulation and the constants against ethical positions that the surrogacy procedure causes in Colombia and other parts of the world.

Paradigm shift in cancer treatment: Cancer treatment as a metabolic disease-fusion of Eastern and Western medicine

Current standard therapies for cancer,including surgery,anti-cancer drugs,and radiotherapy,are thought to contribute to the improvement in the survival rates of cancer patients.However,such standard therapies have 3 major problems:in advanced cancers,it is unlikely that standard cancer treatments will cure the disease;adverse side effects that accompany standard cancer treatments put many patients in distress;and a large amount of medical expenditure is required for new and expensive anti-cancer drugs.These problems may be viewed as a result of establishing treatments without any consideration regarding the root cause of the cancer.Otto Warburg suggested that particular changes in the energy metabolism of cells,which are associated with a shortage of oxygen,are the root cause of cancer.Cancer cells have unique metabolic characteristics,and thus we believe that it is important to treat cancer as a metabolic disease.More specifically,not only is it important to suppress cancer cell metabolism,but it is also important to improve the chronic inflammation that is associated with the development and progression of cancer,and to support the functions of immune cells.This type of view of cancer treatment coincides with the principles of Chinese medicine,which has a history of 4000 years,such as 'fuzheng quxie' and 'zhibing qiuben',which can assist in the establishment of cancer treatments for patients.In this article,we discuss cancer treatments from the view of cancer as a metabolic disease and their association with Chinese medicine,and introduce some clinical cases along with a review of the literature.

Perception of Anemic Women Instead of Herbal Medicine and Dietetics in Treatment of Nutritional Anemia

The iron deficiency anemia is relatively common among young women in Tunisia. Phytotherapy has a place in the treatment of this deficiency anemia. Objective: The objective of this work is to describe the perception of anemic women vis-à-vis the use of herbs and dietary and adapted through a survey in Greater Tunis. Method: A questionnaire survey was conducted among 124 anemic women, recruited from public health facilities in Greater Tunis. Results: The majority of women surveyed (84.7%) had secondary or university education, 10.5% primary and 4.8% were illiterate. Among the women surveyed, 93.5% received a replacement iron-based medical treatment. Among the iron-rich foods, they are legumes that were most appreciated by almost all respondents. While food sources of vitamin B12 and folate were ignored by the majority of women (68%). Two out of three women were unaware of the importance of meat products as the main source of iron, vitamin B12 and folate. Almost half of the women had the habit of consuming tea every day just after meals and they convict that increases the amount of blood. The frequency of the use of traditional medicinal plants by women surveyed in order to treat their anemia was 40%. These women were often advised to use plants by other anemic women and traditional herbalists whose skills in this area were acquired by experience and transmitted from father to son without adequate scientific training. The plants most frequently used were fenugreek, cumin, oregano, rosemary and parsley. Conclusion: These data clearly found the need to intervene for better education of women and girls by the establishment of a nutrition education program associated with other environmental actions. If herbal keeps a place in iron deficiency anemia, the practice of herbal medicine and the preparation of its remedies require the acquisition of institutional competence within the public health authorities whose training must be constantly updated.

The Role of a Pharmacist in the Analysis of Adherence Rates and Associated Factors in HIV-Patients Registered on Centralized Chronic Medicines Dispensing and Distribution(CCMDD)Programme in the Public Sector in South Africa

The study assessed adherence rates and associated factors in Human Immunodeficiency Virus(HIV)patients registered on the Chronic Medicines Dispensing and Distribution(CCMDD)programme in the public Primary Health Care(PHC)set in South Africa(SA)and the role a pharmacist could be played in ARV adherence.Data were collected from 100 HIV-infected patients during a descriptive cross-sectional study using a standardized-questionnaire and face-to-face-exit interviews.Pill-counts technique was performed and adherence-rate of 95%considered acceptable.Data were analyzed using SPSS 22.0.Univariate factors associated with poor-adherence to Highly Active Antiretroviral Therapy(HAART)were assessed using ANOVA and a p≤0.05 is considered statistically significant.Of 100 HIV-infected,74 were females and 26 males with mean-age(±SD)of 38.98(±9.24)years enrolled on HAART for more than 36 months.Of these,26 and 36 were on WHO stages 2 and 3 respectively.Adherence-rates computed from 76 patients revealed 43(56.6%)having poor adherence-rate and 33(43.4%)with acceptable adherence rate.Of the demographic factors analyzed age and educational background had an influence on adherence rates with p=0.087 and 0.097 respectively.Other factors associated with acceptable adherence were:WHO staging(p=0.016),recent CD4 count(p=0.07),adverse effects(p=0.073),stigma(p=0.027).Of the different areas with waiting times,reception and pharmacy were statistically significant with p=0.095 and 0.042 respectively.

Penetrating Ocular Trauma in a Goldfish Model after Chloramphenicol or Traditional Medicine Angong Niuhuang Pill Treatment: An Analysis of Retinal Responses after 7 Days

Purpose: While there were numerous clinical examples of ocular damage, the histopathology of retinal responses was poorly characterized, and animal model research was limited. The consequences of retinal lesions with traditional medicine treatment were mostly unknown. In this work, goldfish was employed as a model for penetrating injury of the eyes to study the ocular trauma with antibiotic and traditional medicine treatments. Materials and Methods: The penetration of the eyes was performed at 2mm above the midline of the limbus in the superior quadrant with an 18-gauge sterile needle, all the way to the retina but avoiding the lens while the animals were anaesthetized in water containing 100 mg/L ethyl 3-aminobenzoate methanesulfonate (MS-222). The animals were divided into three groups and received treatments of saline, chloramphenicol, and Angong Niuhuang pill (Angong) eyedrops twice a day respectively. Angong after seven days, the animals were sacrificed. Immunohistochemical evaluation of proliferative cell nuclear antigen (PCNA), brain-derived neurotrophic factor (BDNF), catalase, and cleaved caspase-3, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) for apoptotic cells were performed on the fish’s superior quadrants of the retinae. The whole experiment was repeated two times. Result: It was evident that both the retinae treated with chloramphenicol and Angong had fewer apoptotic cells and more proliferative cells, particularly in the cases of the Angong treatment. BDNF was in the inner nuclear layer and ganglion cell layer of all groups. In the chloramphenicol and Angong groups, some cells in the outer nuclear layer displayed BDNF. Catalase reactions confirmed equivalent findings that the treated retinae with chloramphenicol or Angong treatment had less catalase. Conclusion: Angong Niuhuang pill is a traditional medicine composite formula with antibiotic and neuroprotective effects on the brain and the eyes, and this work also pointed out its possible pharmaceutical potential.

Epidemiological, Clinical, Paraclinical and Evolutionary Aspects of Urinary Tract Infection in Diabetics Hospitalized at the Department of Medicine of Abass Ndao Hospital from January 01, 2018, to December 31, 2018

Introduction: Urinary tract infection (UTI) is a major public health problem because of its morbidity and mortality. It occurs with increased frequency during diabetes. The objective of this work was to study the frequency and etiologies of urinary tract infections in diabetics hospitalized at the department of medicine of Abass Ndao Hospital. Patients and Methods: This work was a cross-sectional, descriptive, and analytical study conducted from January 01, 2018, to December 31, 2018. It focused on hospitalized diabetic patients with urinary tract infection. Epidemiological, clinical, and evolutionary data of UTI were evaluated. Results: One hundred and twenty-eight (128) diabetic patients had a cytobacteriological urine exam (CUE). 44 of who had a positive CUE (34.4%). The age group [60 - 69] years was the most represented (31.8%). Women predominated (61.4%) with a sex ratio (m/f) of 0.63. Abdominal pain was the most frequent reason for consultation, followed by polydipsia. Fever was recorded in 21 patients (47.7%). Type 2 diabetes was found in most patients (70.5%). Glycemia above 2g/l was found in 34 patients (89.5%). Anemia accounted for more than half of the patients with 29 cases (65.9%). Leukocytosis was noted in 28 patients (63.6%) and a positive CRP in 33 patients (75%). An increase in urea-creatinine was noted in 23 cases (52.3%). The results of the CUE revealed Escherichia coli as predominant (43.2%, n = 19), followed by Candida with 22.7% (n = 10). Antibiotic therapy was given to all patients. The mostly used antibiotic in the treatment of UTI was Cefotaxime 27.3% (n = 12). Older age and female gender were associated with the presence of E. coli. Four (4) deaths were recorded (9%). They were all male over the age of 65. Conclusion: UTI in diabetes is an important cause of morbidity and mortality. The development and implementation of a prevention and management program are essential.

Seeing beneath the surface:Harnessing point-of-care ultrasound for internal jugular vein evaluation

Point-of-care ultrasound(POCUS)of the internal jugular vein(IJV)offers a noninvasive means of estimating right atrial pressure(RAP),especially in cases where the inferior vena cava is inaccessible or unreliable due to conditions such as liver disease or abdominal surgery.While many clinicians are familiar with visually assessing jugular venous pressure through the internal jugular vein,this method lacks sensitivity.The utilization of POCUS significantly enhances the visualization of the vein,leading to a more accurate identification.It has been demonstrated that combining IJV POCUS with physical examination enhances the specificity of RAP estimation.This review aims to provide a comprehensive summary of the various sonographic techniques available for estimating RAP from the internal jugular vein,drawing upon existing data.

Metabolic disease and the liver: A review

Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin America.The presence of metabolic comorbidities coexisting with liver disease varies substantially among populations.It is acknowledged that obesity is boosting the type 2 diabetes mellitus“epidemic,”and both conditions are significant contributors to the increasing number of patients with MASLD.Nonalcoholic steatohepatitis represents a condition of chronic liver inflammation and is considered the most severe form of MASLD.MASLD diagnosis is based on the presence of steatosis,noninvasive scores and altered liver tests.Noninvasive scores of liver fibrosis,such as serum biomarkers,which should be used in primary care to rule out advanced fibrosis,are simple,inexpensive,and widely available.Currently,guidelines from international hepatology societies recommend using noninvasive strategies to simplify case finding and management of high-risk patients with MASLD in clinical practice.Unfortunately,there is no definite pharmacological treatment for the condition.Creating public health policies to treat patients with risk factors for MASLD prevention is essential.

Current perspectives of viral hepatitis

Viral hepatitis represents a major danger to public health,and is a globally leading cause of death.The five liver-specific viruses:Hepatitis A virus,hepatitis B virus,hepatitis C virus,hepatitis D virus,and hepatitis E virus,each have their own unique epidemiology,structural biology,transmission,endemic patterns,risk of liver complications,and response to antiviral therapies.There remain few options for treatment,in spite of the increasing prevalence of viral-hepatitiscaused liver disease.Furthermore,chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality,even though effective treatments are available that could reduce or prevent most patients’complications.In 2016,the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030,along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis.Today,treatment is sufficiently able to prevent the disease from reaching advanced phases.However,future therapies must be extremely safe,and should ideally limit the period of treatment necessary.A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis.This review aims to summarize the current state of knowledge on each type of viral hepatitis,together with major innovations.

Promising use of metformin in treating neurological disorders:biomarker-guided therapies

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available today.Since most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism.However,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders.Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders.These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted therapy.In this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

Update in lean metabolic dysfunction-associated steatotic liver disease

BACKGROUND A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD).They are now defined as metabolic dysfunction-associated steatotic liver disease(MASLD),which includes cardiometabolic criteria in adults.This condition,extensively studied in obese or overweight patients,constitutes around 30%of the population,with a steady increase worldwide.Lean patients account for approximately 10%-15%of the MASLD population.However,the pathogenesis is complex and is not well understood.AIM To systematically review the literature on the diagnosis,pathogenesis,characteristics,and prognosis in lean MASLD patients and provide an interpretation of these new criteria.METHODS We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023,specifically focusing on lean NAFLD,MAFLD,or MASLD patients.We include original articles with patients aged 18 years or older,with a lean body mass index categorized according to the World Health Organization criteria,using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian population.RESULTS We include 85 studies in our analysis.Our findings revealed that,for lean NAFLD patients,the prevalence rate varied widely,ranging from 3.8%to 34.1%.The precise pathogenesis mechanism remained elusive,with associations found in genetic variants,epigenetic modifications,and adaptative metabolic response.Common risk factors included metabolic syndrome,hypertension,and type 2 diabetes mellitus,but their prevalence varied based on the comparison group involving lean patients.Regarding non-invasive tools,Fibrosis-4 index outperformed the NAFLD fibrosis score in lean patients.Lifestyle modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles,with some medications showing efficacy to a lesser extent.However,lean NAFLD patients exhibited a worse prognosis compared to the obese or overweight counterpart.CONCLUSION MASLD is a complex disease comprising epigenetic,genetic,and metabolic factors in its pathogenesis.Results vary across populations,gender,and age.Limited data exists on clinical practice guidelines for lean patients.Future studies employing this new nomenclature can contribute to standardizing and generalizing results among lean patients with steatotic liver disease.