COVID-19: Clinical aspects and therapeutics responses

COVID-19 has created havoc in the world by causing thousands of demises in a short period of time. Up till now, several attempts have been made for potential therapeutics against SARS-COV2. In this retrospective, single-center study, we extracted data from 122 COVID-19, RT-PCR confirmed patients. who were treated with a new treatment strategy of lianhuaqingwen with Arbidol Hydrochloride. The patients were either asymptomatic or had mild symptoms for COVID-19 disease. Of 122 patients 21 (17.21%) patients developed severe conditions of COVID-19, while total 111 (90.9%) experienced mild symptoms such as fever in 93 (76.22%) patients, cough in 23 (20.17%) and muscle pain were observed in total 8 (7%) patients. Furthermore our newly applied drugs combination (Lianhuaqingwen and Arbidol Hydrochloride) showed therapeutic effects in 5–7 days in patients with mild symptoms with 98% recovery rate. These results indicate that COVID-19 patients with mild symptoms can be treated with Lianhuaqingwen and Arbidol Hydrochloride. However, extensive clinical investigations are required to confirm the effectiveness of these drugs.     

The fate of fenclozic acid in the gut and its effect on some aspects of gut metabolism

1. In the rat [¹⁴C]fenclozic acid is not metabolized in the gut and passes into the portal blood unchanged.

2. After intraduodenal administration of [¹⁴C]fenclozic acid, a small proportion of the dose binds to high molecular weight substances in the gut wall.

3. The incorporation of L-[U-¹⁴C]leucine and N-[³H]acetyl-D-glucosamine into acid-precipitable materials by isolated mucosal cells and homogenates of gut mucosal cells was inhibited by fenclozic acid in a dose-dependent manner.

4. Other non-steroidal anti-inflammatory drugs (indomethacin, phenylbutazone, pred-nisolone, salicylic acid and paracetamol) were tested for their potency as inhibitors of glycoprotein production by whole cell preparations and by homogenized gut cell preparations. Marked differences were observed in the inhibitory potency of indomethacin, paracetamol and salicylic acid in the two experimental systems.

5. Fenclozic acid had no major effect on the rate of total glycoprotein production by the isolated perfused rat liver or by the doudenal mucosa in situ.

6. Fenclozic acid displaces albumin-bound [³H]tryptophan and increases the level of hepatic tryptophan pyrrolase approx. threefold. The inhibition of gut glycoprotein production by fenclozic acid was not prevented by free tryptophan.     

Neuroendocrinology of insulin resistance: metabolic and endocrine aspects of adiposity

Abdominal obesity is a major risk factor to attract the insulin resistance syndrome. It is proposed that abdominal obesity exposes the liver to elevated levels of free fatty acids, which activate a neuroendocrine reflex, leading to increased circulating levels of glucocorticoids. Besides directly attenuating peripheral insulin signaling, glucocorticoids oppose the activity of central nervous regulatory systems that stimulate insulin action. Among the factors that promote insulin action is leptin. Leptin regulates peripheral fuel partitioning and insulin action mainly through hypothalamic neuronal networks, which in turn, regulate endocrine activity of adipose tissue in a way comparable to thiazolidinediones. These are a class of insulin-sensitizing drugs, which exert their antidiabetic effects through the gamma isoform of peroxisome proliferator-activated receptor (PPAR-γ). Since glucocorticoids oppose leptin action at several levels of control (including the central nervous system, CNS), it is argued that subjects easily develop obesity and associated metabolic disorders.     

药物与天然产物:从动植物到人类疾病的治疗（英文）

Plants toxic to livestock species have a significantly negative impact on agriculture but can be an important source of bioactive molecules for use in medicine.The initial research on plant toxicity is focused on the response to the poisoning and the specific livestock species impacted by the toxic plant.This research emphasizes the identification of the plant and natural product(s)responsible for the toxicity to livestock,the prevention of further poisonings,and the development of treatments for the affected animals.Once the bioactive molecules impacting the livestock species have been identified,research on these compounds is then focused on determining the mechanism of action,the development of models for further study,and the identification of potential drug candidates for the treatment of disease.Specific examples of the agricultural-based research that are relevant to Human and Veterinary Medicine include:cyclopamine from Veratrum californicum(western false hellebore),piperidine alkaloids fromLupinus species(lupines),and cicutoxin from Cicuta species(water hemlock).     

The gut microbiota and lipid metabolism: implications for human health and coronary heart disease

Coronary heart disease (CHD) is the leading cause of mortality in Western societies, affecting about one third of the population before their seventieth year. Over the past decades modifiable risk factors of CHD have been identified, including smoking and diet. These factors when altered can have a significant impact on an individuals' risk of developing CHD, their overall health and quality of life. There is strong evidence suggesting that dietary intake of plant foods rich in fibre and polyphenolic compounds, effectively lowers the risk of developing CHD. However, the efficacy of these foods often appears to be greater than the sum of their recognised biologically active parts. Here we discuss the hypothesis that beneficial metabolic and vascular effects of dietary fibre and plant polyphenols are due to an up regulation of the colon-systemic metabolic axis by these compounds. Fibres and many polyphenols are converted into biologically active compounds by the colonic microbiota. This microbiota imparts great metabolic versatility and dynamism, with many of their reductive or hydrolytic activities appearing complementary to oxidative or conjugative human metabolism. Understanding these microbial activities is central to determining the role of different dietary components in preventing or beneficially impacting on the impaired lipid metabolism and vascular dysfunction that typifies CHD and type II diabetes. This approach lays the foundation for rational selection of health promoting foods, rational target driven design of functional foods, and provides an essential thus-far, overlooked, dynamic to our understanding of how foods recognised as "healthy" impact on the human metabonome.     

From mouse genetics to human therapeutics

This review examines how and where genomic and genetic research will impact pharmaceutical research and development, and emphasizes how mouse genomics and genetics can improve the understanding of human disease pathobiology and drug metabolism, and identify new targets for therapeutic intervention. Although important discoveries can be made from mouse genetic analysis, its utility has been limited by the high cost and long time lines required for such research. A recently developed computational method that markedly accelerates the pace of genetic discovery and reduces its cost is also described.     

Emerging aspects of nanotoxicology in health and disease: From agriculture and food sector to cancer therapeutics

Nanotechnology is an evolving scientific field that has allowed the manufacturing of materials with novel physicochemical and biological properties, offering a wide spectrum of potential applications. Properties of nanoparticles that contribute to their usefulness include their markedly increased surface area in relation to mass, surface reactivity and insolubility, ability to agglomerate or change size in different media and enhanced endurance over conventional-scale substance. Here, we review nanoparticle classification and their emerging applications in several fields; from active food packaging to drug delivery and cancer research. Nanotechnology has exciting therapeutic applications, including novel drug delivery for the treatment of cancer. Additionally, we discuss that exposure to nanostructures incorporated to polymer composites, may result in potential human health risks. Therefore, the knowledge of processes, including absorption, distribution, metabolism and excretion, as well as careful toxicological assessment is critical in order to determine the effects of nanomaterials in humans and other biological systems. Expanding the knowledge of nanoparticle toxicity will facilitate designing of safer nanocomposites and their application in a beneficial manner.     

Historical review: Cytokines as therapeutics and targets of therapeutics

Cytokine research has spawned the introduction of new therapies that have revolutionized the treatment of many important diseases. These therapeutic advances have resulted from two very different strategies. The first therapeutic strategy embodies the administration of purified, recombinant cytokines. The second relies on the administration of therapeutics that inhibit the harmful effects of upregulated, endogenous cytokines. Examples of successful cytokine therapeutics include hematopoietic growth factors (colony stimulating factors) and interferons. Prime examples of cytokine antagonists that have profoundly altered the treatment of some inflammatory disorders are agents that inhibit the effects of tumor necrosis factor (TNF). In this article, we highlight some of the studies that have been responsible for the introduction of cytokine and anti-cytokine therapies, with emphasis on the development of interferons and anti-TNF agents.     

Species-specific and age-dependent bile acid composition: aspects on CYP8B and CYP4A subfamilies in bile acid biosynthesis

The present review aims to give an overview of the cytochrome P450 8B (CYP8B) and cytochrome P450 4A (CYP4A) subfamilies in relation to biosynthesis of bile acids, in particular trihydroxy bile acids. Trihydroxy bile acids are basically required in most species and have an impact on cholesterol and lipid metabolism. The primary trihydroxy bile acid in most mammals is cholic acid. Some species produce other important trihydroxy bile acids, for example the adult pig which produce hyocholic acid instead of cholic acid. The position of the third hydroxyl group in cholic acid and hyocholic acid, 12alpha or 6alpha position, respectively, has a profound effect on the hydrophilic-hydrophobic property of the trihydroxy bile acids. The CYP8B subfamily is required for introduction of the 12alpha-hydroxyl group in cholic acid biosynthesis. The enzyme responsible for 6alpha-hydroxylation in hyocholic acid biosynthesis, however, varies among species. This review will discuss, in particular, porcine members of the CYP8B and CYP4A subfamilies because interesting findings regarding members of these subfamilies have recently been recognized in this species. CYP8B1 was for a long time believed to be absent in the pig but was recently found to be expressed in fetal pig liver. The enzyme catalyzing the 6alpha-hydroxylation in hyocholic acid biosynthesis in pig was found to be an atypical member of the CYP4A subfamily, denoted CYP4A21. The review presents bile acid biosynthesis in view of these findings and discusses physiochemical properties and developmental-dependent aspects related cholic acid and hyocholic acid biosynthesis.     

Mining PeptideAtlas for biomarkers and therapeutics in human disease

Mass spectrometry information has long offered the potential of discovering biomarkers that would enable clinicians to diagnose disease, and treat it with targeted therapies. PeptideAtlas currently provides access to large-scale spectra data and identification information. This data, and the generation of targeted peptide information, represents the first step in the process of locating disease biomarkers. Reaching the goal of clinical proteomics requires that this data be integrated with additional information from disease literature and genomic studies. Here we describe PeptideAtlas and associated methods for mining the data, as well as the software tools necessary to support large-scale integration and mining.     

Targeting hepatitis B virus and human papillomavirus induced carcinogenesis: novel patented therapeutics

Viral infections leading to carcinogenesis tops the risk factors list for the development of human cancer. The decades of research has provided ample scientific evidence that directly links 10-15% of the worldwide incidence of human cancers to the infections with seven human viruses. Moreover, the insights gained into the molecular pathogenetic and immune mechanisms of hepatitis B virus (HBV) and human papillomavirus (HPV) viral transmission to tumour progression, and the identification of their viral surface antigens as well as oncoproteins have provided the scientific community with opportunities to target these virus infections through the development of prophylactic vaccines and antiviral therapeutics. The preventive vaccination programmes targeting HBV and high risk HPV infections, linked to hepatocellular carcinoma (HCC) and cervical cancer respectively have been recently reported to alter age-old cancer patterns on an international scale. In this review, with an emphasis on HBV and HPV mediated carcinogenesis because of the similarities and differences in their global incidence patterns, viral transmission, mortality, molecular pathogenesis and prevention, we focus on the development of recently identified HBV and HPV targeting innovative strategies resulting in several patents and patent applications.     

Antibiotics as both friends and foes of the human gut microbiome: The microbial community approach

The exposure of the human gut to antibiotics can have a great impact on human health. Antibiotics pertain to the preservation of human health and are useful tools for fighting bacterial infections. They can be used for curing infections and can play a critical role in immunocompromised or chronic patients, or in fighting childhood severe malnutrition. Yet, the genomic and phylogenetic diversity of the human gut changes under antibiotic exposure. Antibiotics can also have severe side effects on human gut health, due to the spreading of potential antibiotic resistance genetic traits and to their correlation with virulence of some bacterial pathogens. They can shape, and even disrupt, the composition and functioning diversity of the human gut microbiome. Traditionally bacterial antibiotic resistances have been evaluated at clone or population level. However, the understanding of these two apparently disparate perspectives as both friends and foes may come from the study of microbiomes as a whole and from the evaluation of both positive and negative effects of antibiotics on microbial community dynamics and diversity. In this review we present some metagenomic tools and databases that enable the studying of antibiotic resistance in human gut metagenomes, promoting the development of personalized medicine strategies, new antimicrobial therapy protocols and patient follow-up.     

Clinical aspects of bile acid metabolism in liver diseases

For a long time, it has been assumed that the liver plays an important role in the formation and excretion of bile acids and that the metabolism of bile acids, therefore, can be disturbed to some extent in liver diseases. Pathophysiological aspects of the disturbed metabolism of bile acids remained obscure at the time when procedures of qualitative and quantitative analyses, identification and estimation of bile acids began to be utilized in practice 20 years ago. Since then, the metabolism of bile acids has been clarified in individuals under normal as well as pathological circumstances. Because of a functionally and morphological close relation between hepatic epithelial cells and the metabolism of bile acids, the pathophysiological aspects of the disturbed metabolism of bile acids in parenchymatous inflammatory diseases of the liver, fatty liver, cholestasis and primary hepatocellular carcinoma are attracting considerable attention. First applied to the measurement of human bile acids in blood plasma in 1965, gas-liquid chromatography has been utilized as a standard method in medical practice. Recently, radioimmunoassay and enzyme linked radioimmunoassay have been utilized. This progress in the estimation of bile acids has awoken our interest in the pathophysiological significance of bile acids in liver diseases. The author reviewed the information on bile acid metabolism in liver diseases which has been reported up to the present.     

Polyphenolic compounds: interactions with the gut and implications for human health

Polyphenolic compounds are abundant throughout the plant kingdom and are found in a wide variety of human foods. The flavonoids, which are the best defined group of polyphenols in the human diet, themselves comprise a large and complex group, all of which contain a three-ring structure with two aromatic centres and a central oxygenated heterocycle. Recent evidence suggests that significant quantities of quercetin and possibly myricetin and kaempferol are absorbed in the gut. A larger fraction probably remains in the lumen, and thus a substantial proportion of the gastrointestinal mucosa is exposed to biologically significant concentrations of these compounds. A substantial body of experimental work has established that flavonoids can suppress carcinogenesis in animal models and there is considerable interest in the biological effects of these compounds at the cellular level. Flavonoids interact with cellular signal pathways controlling the cell cycle, differentiation and apoptosis. Their potentially antineoplastic effects include antioxidant activity, induction of Phase II enzyme activity, inhibition of protein kinases and interactions with Type II estrogen binding sites. Naturally occurring polyphenolic compounds may play a role in the protective effects of fruits and vegetables against cancers in general, and they appear to have considerable potential for pharmaceutical uses as chemopreventive agents against neoplastic changes in the alimentary tract. Future research should therefore focus on the biological effects of flavonoids in the human body, using biomarkers to define their effects at each stage in the onset of neoplasia.