Infectious disorders drug targets最新文献

Pimples, blackheads, whiteheads, etc., are common types of acne that pop up on the skin each time, whenever dead cells and oils obstruct the outgrowth of hair from the hair follicle. It is very common to observe this condition in teenagers, but regardless of age, if the causing condition is met, acne can occur at any point in life. The characteristic feature of all types of acne is it starts with inflammation of the skin. These inflammatory marks (like black spots, pores, small scars, etc.) leave behind even when acne disappears. Plants like vegetables and flowers are naturally rich in different types of polyphenolic compounds called flavonoids. These flavonoids have various key functions, from guiding cell movement to maintaining oxidative pressure in the body. In this study, we discuss six types of flavonoids that have the potential to be used as med-icine for the treatment of different kinds of skin breakouts. Moreover, the result of molecular docking of different proteins that have an association with acne is also discussed.

Mitochondria, also called 'powerhouse of the cell', is meant for energy generation in eukaryotic cells. This action is performed by mitochondria through the oxidative phosphor-ylation (OXPHOS) of the respiratory chain (RC). Based on the functioning of the cell, the number of mitochondria varies up to thousands in number. Mutations in the mitochondrial DNA (mtDNA) and/or nuclear DNA (nDNA) genes may lead to the generation of primary mitochondrial disease (PMD) that affects the structure and function of mitochondria. The di-agnosis of such mitochondrial diseases occurs in early childhood and it can lead to serious, fetal and multi-organ diseases. Understanding epigenetic events and changes in the pathway can help improve the effectiveness of treatment. However, there are several reasons lack of the disease symptoms (age, sign, symptoms, morbidity and lethality), restricted availability of pre-clinical models along with extensive phenotypes that hamper the development of efficient drugs. Despite the introduction of new treatments and the encouraging results of treatments and therapies, there is no effective cure for PMD. This article contains information about the changes associated with cytopathic diseases that make possible the analysis of various diseases by genetic techniques. Increasing our under-standing of how mitochondrial DNA mutations affect mitochondrial metabolism and subse-quently result in neurodegenerative disease will prove vital to the development of targeted therapies and treatments.

Background: Clostridium difficile is an opportunistic infection that can lead to antibi-otic-associated diarrhea and toxic megacolon.

Objective: This systematic review study aimed to investigate polyphenols' antibacterial and anti-toxin properties and their effects on reducing complications related to C. difficile Infections (CDI).

Methods: This systematic review was conducted following the PRISMA guideline 2020. Multiple databases, including Web of Science, PubMed, Cochrane Library, EMBASE, and Scopus, were searched thoroughly for existing literature. After considering the inclusion and exclusion criteria for the review, 18 articles were included. Data were collected and registered into an Excel file for further investigations and conclusions.

Results: Polyphenols by reducing Reactive Oxygen Species (ROS) levels, increasing inflammatory factor Interleukin 10 (IL-10), reducing Nuclear Factor kappa B (NF-κB) and Tumour Necrosis Fac-tor-α (TNF-α), IL-6, IL-1α, IL-1β, Granulocyte Colony-stimulating Factor (G-CSF), and Monocyte Chemoattractant Protein-1 (MCP-1) and Macrophage Inflammatory Protein-1 alpha (MIP-1α) lev-els, and regulating the expression of Bcl-2 and Bax, make the growth and replication conditions of C. difficile more difficult and prevent it from producing toxins. Furthermore, polyphenols can ex-hibit prebiotic properties, promoting the growth of beneficial Bifidobacterium and Lactobacillus species and consequently regulating gut microbiota, exerting antimicrobial activities against C. dif-ficile. They also induce their beneficial effects by inhibiting the production of C. difficile TcdA and TcdB.

Conclusion: Polyphenols have been reported to inhibit C. difficile growth and toxin production by several mechanisms in preclinical studies. However, more clinical studies are needed to investigate their safety in humans.

Tuberculosis (TB) spreads through droplets that contain Mycobacterium tuberculosis (Mtb) and can infect susceptible people. Due to different risk factors, people have different susceptibility ranges towards TB. The risk factors are classified into three main groups, includ-ing bacterial, environmental, and host factors. Literature review reveals that the most important host risk factors are aging, male gender, genetics, epigenetics, having an impaired immune system, diabetes, malignancy, malnutrition, anemia, and pregnancy. The risk factors contribute to the increase in TB cases through inflammation, increased contact with TB patients, disrup-tion of immune genes, changes in gene expression, increased activity of Mtb, damage to cellu-lar immunity, reactivation of Latent TB Infection (LTBI), increased susceptibility to TB, com-promised immunity, and changes in the proportion of T cell subgroups, respectively. Therefore, identification of the infection source and high-risk people and timely treatment of the patients can reduce TB mortality and help control the disease.

Background: Tuberculosis is an infectious disease caused by Mycobacterium tuber-culosis. The current treatment protocols for pulmonary tuberculosis are quite effective, even though the treatment requires 3-6 months. The current treatment protocols for extrapulmonary tuberculosis are based on the same drugs that are used for pulmonary tuberculosis. However, the success rates are much lower for certain types of extrapulmonary tuberculosis, such as tubercu-lous meningitis. Tuberculous meningitis is one of the very few diseases attributable to bacteria that have a very high short-term mortality rate among diagnosed patients, even after treatment with antibiotics that are effective for pulmonary tuberculosis. For example, rifampicin is highly effective for the treatment of pulmonary tuberculosis, but its effectiveness for the treatment of tuberculous meningitis is much lower. The reason for the lower effectiveness of rifampicin against tuberculous meningitis is that it has low Blood-Brain Barrier (BBB) permeability, which results in lower concentrations of the drug at the required sites in the central nervous system.

Methods: In this work, ligands having improved BBB permeability and pharmacokinetic and pharmacodynamic properties, either similar to or better than that of rifampicin, have been designed. The BBB permeability of the designed molecules was assessed by using pkCSM, a machine-learning model. Pharmacokinetic properties, drug-likeness, and synthesizability were assessed by using SWISS-MODEL. The binding affinity of the designed drugs was assessed by using AutoDock Vina. A customized scoring function, StWN score, was used for a quantitative weighted assessment of all the properties of interest to rank the designed molecules.

Results: In this study, drug-like ligands have been designed that have been predicted to have high BBB permeability as well as high affinity for RNA polymerase β of Mycobacterium tuberculosis.

Conclusion: The best ligands generated by the tools employed were selected as potential drugs to address the current need for better options for the treatment of tuberculous meningitis.

Background: Microorganisms associated with sea sponges have proven to be good natural product resources that are biologically active and pharmaceutically important.

Objective: This research aimed to identify actinomycetes related to a sponge from Bar-ranglompo Island Makassar and the antibacterial compounds.

Methods: Identification of actinomycetes was based on molecular characterization of sequence gen16S rRNA. The antibacterial compound was separated using vacuum liquid chromatog-raphy and preparative Thin Layer Chromatography (TLC). The structure determination was done based on spectroscopy 1H-NMR, 13C-NMR, 2D NMR, and mass spectra.

Results: Molecular characterization showed that actinomycetes strain BLP 20 had the closest relationship with Streptomyces parvulus and Uncultured Streptomyces sp. with a similarity value of 83%. The results obtained from the characterization of antibacterial compounds based on spectroscopic data indicate that these compounds lead to Actinomycin D.

Conclusion: Characterization and identification of Strain 20 / BLP by molecular phylogenetic analysis of 16S rRNA sequences revealed the closest relationship with Uncultured Streptomy-ces sp and S. parvulus with a similarity value of 83 %, which indicated a new species. The structure of the active compound isolated from actinomycetes strain 20 / BLP leads to Actino-mycin D.

It is a known fact that HIV infection remains a serious public health problem throughout the world, and the need to constantly develop new antiretroviral drugs to combat HIV emerges from the fact that repetitive mutations occurring in viral enzymes make this virus resistant to antiretroviral drugs. This resistance causes failure of treatment, and hence, for many years, extensive research has been to discover newer possibilities for fighting this disease at a molecular level, along with many long-standing and expensive clinical trials. Many scientific research programs have either been discarded or unsuccessful. However, the research has not stopped, and in the process, many heterocyclic scaffolds have been used to build up novel drug molecules to combat this disease. A literature survey reveals that many heterocycles have been explored and were found to be very useful in treating different types of viral infections. This concise and rigorous literature explains the journey and highlights the various strategies to develop new anti-HIV drug candidates.

Hygiene has been identified as an important step in anticipating health-related pol-lution, with conflicting reports about consistent sanitation standards in the nation. This narrative review of published studies has led to the discussion of hand hygiene and health practices, as well as the identification of necessary methods that are available in low and middle-income countries. An effective survey of accessible information is conducted in this way based on re-view questions. A number of 372 articles were found on the web, and 32 articles were used in the final analysis. Overall, the standard of hand hygiene is set at 20.49%. Difficulties identified for the people in low or middle-income countries are poor awareness and sound information about hand hygiene, lack of resources including water, soap, hand scrubbing gel, etc., as mis-interpretations related to hand hygiene practices. People are paying more attention to healthcare-related illnesses as it becomes increasingly clear that most of them may be pre-vented. The free evidence-based practice states that to lower the danger of contamination, hand hygiene should be properly adhered to. The difficulties recognized in this review are reliable, with the discoveries of studies that have been led somewhere else. By conducting a basic ex-amination of the "Clean Care is Safer Care" as an excellent arrangement of WHO's global initiative activity on patient well-being programs, developing nations will have more time to consider the essential approaches for the use of fundamental disease prevention exercises in our health care settings.