Recent Advances in Inflammation & Allergy Drug Discovery最新文献

Introduction: The worldwide impact of the foodborne pathogen Salmonella can never be overstated, nor can be the fatal threat of septicemia in patients infected with its Typhimurium serovar. Behind the hyperimmune response in the case of septicemia lies a critical phenomenon of the bacterial pathogenic signals being sensed by different pattern recognition receptors, such as the Typhimurium effector proteins that are detected by toll-like receptors.

Methods: To mitigate such a threat, precise structural and functional description of these effectors is necessary. The same has been addressed in this article using accelerated biocomputational techniques, beginning with the identification of the functional niche of the effectors and their influence over other proteins.

Results: The molecular crystal structures were retrieved, and rigorous molecular docking experiments were conducted among the TLRs and effector proteins in order to examine the interactions. The interactions were thereby evaluated and screened according to their respective strengths using parameters including binding affinity, dissociation constant, hydropathy variation, etc. SopB effectors were found to be detected by three different TLR proteins and GtgE by two other TLRs, while SifA, SrfJ, and SsaV had only a single interacting TLR partner each. Interestingly, TLR9 presented lower sensitivity towards PAMPs of this bacterium.

Conclusion: Normal modal analyses in combination with atomistic molecular dynamics simulations that tend to imitate natural cytosolic environments reveal stable and consistent interactions and realistic conformations among the effector-bound TLR complexes. The findings open up new avenues for the development of targeted therapies against Salmonella, which could significantly reduce the global burden of this foodborne pathogen.

Inflammation is a defense mechanism of the body against harmful stimuli/organisms. Even if it is the body's defense mechanism, these mediators may affect different ways in the human body and can lead to chronic disorders. The most common treatment strategy for the acute type of inflammation mainly includes synthetic chemical drugs; Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and immunosuppressant drugs whereas these synthetic drugs have many side effects, adverse effects, and limitations. Herbal drugs can be a promising alternative to these synthetic drugs but they too have limitations. Recent advances in the nanotechnology field can be combined with herbal drugs to overcome the limitations. Research works done on topical nanophyto pharmaceuticals for anti-inflammatory activity were compiled and in all the studies, clear evidence is indicated for the increased penetration, distribution, and increased efficacy of phytopharmaceuticals when formulated into nano dosage forms. Considering the adverse effects and limitations of most widely used synthetic drugs, topical nano Phyto pharmaceuticals can play a pivotal role in the local and systemic delivery of promising phytoconstituents to a specific site of the body.

Background and objective: The COVID-19 pandemic is a recent global issue with no established consensus on treatments. Therefore, the aim of this study was to assess the impact of corticosteroid (CS) pulses on the prognosis of COVID-19 patients admitted to hospitals.

Methods: In this retrospective single-center cross-sectional study, we used hospital records of all consecutive patients aged 18 years or older admitted to the hospital from July 23rd to September 23rd, 2021. All patients included in the study had confirmed SARS-CoV-2 infection using polymerase chain reaction (PCR) testing and required hospitalization. Demographic and clinical information, as well as patient outcomes, were collected. Treatment details, including the type(s), cumulative doses, and duration of administered corticosteroids, were also recorded. CS pulse therapy was defined as the daily administration of 24 mg or more of dexamethasone or its equivalents.

Results: A total of 500 patients with COVID-19 were included in this study, comprising 122 patients who received CS pulse therapy and 378 patients who did not. A higher mortality rate was observed in patients receiving CS pulse therapy (42.6%) compared to the other group (28%) (p =0.04). Additionally, logistic regression analysis showed an increased mortality risk in patients receiving CS pulse therapy in the crude model (OR=1.54, 95% CI: 1.01-2.27, p <0.01). However, after adjusting for confounding factors, such as mechanical ventilation and ICU admission, the results were reversed (OR=0.21, 95% CI: 0.07-0.62, p <0.01). ; Conclusion: In the findings of the current study, treatment with CS pulses was shown to significantly enhance recovery in patients with non-severe COVID-19.

Background: SARS-CoV-2 infection has mild and asymptomatic to critical clinical course affecting mainly the lungs. Few case reports of COVID-19-associated pancytopenia are reported, but a series of 18 cases is not described in the literature to date.

Aims and objectives: This study aimed to investigate pancytopenia in COVID-19 and its correlation with severity and to explore the detailed clinical and biochemical information in COVID-19- associated pancytopenia. This study also highlights pancytopenia's rarity and prognostic value among COVID-19 patients.

Materials and methods: This was a retrospective observational study conducted in a tertiary care centre at a level 3 COVID care facility that included adults of either sex having positive RT PCR for COVID-19 from October 2020 to May 2021. Data were collected from the online outpatient department and hospitalized patients.

Results: A total of 18 cases were included in the study; 13 were males (72.2%). The mean age was calculated as 48.56 years. Cases were categorized as severe 13 (72.2%) and non-severe 5 (27.8%) disease on the first day of pancytopenia. The most common presentations were fever 18 (100%) and cough 18 (100%), followed by generalized weakness 16 (88.9%), breathlessness 15 (83.3%), and diarrhoea 10 (55.6%). One case died in the severe disease group. The mean of haemoglobin, leukocyte count, and platelets in severe vs non-severe disease were calculated as 8.59 vs 8.74, 2339 vs 2578, and 77769 vs 88600, respectively.

Conclusion: Pancytopenia was more prevalent in severe disease and age group 40-60 years. CAP was most likely due to secondary bone marrow suppression. It has no prognostic value for disease outcomes.

Anti-inflammatory therapies currently in use mainly include steroidal and non-steroidal drugs. Contrary to their side effects, the steroid hormones glucocorticoids, which are synthetic versions of natural cortisol, are nevertheless often employed to treat a variety of inflammatory disorders. Other drug class of choice is non-steroidal drugs which mainly target COX-2 and hence the synthesis of prostaglandins, particularly PGE2. To cure both the short-term effects of chronic inflammatory disorders and the long-term symptoms of acute inflammation, pharmaceutical chemists are in continuous search for more potent and less toxic agents. Apart from these two drug classes, phytochemicals are gaining the attention of researchers as source of alternative antiinflammatory agents. However, every drug class has its own advantages or disadvantages thus requiring intervention of newer approaches. Currently, drugs used for anti-inflammatory therapies are costly with low efficacy, high health risk, and socio-economic impact due to the concern issue of their toxicity. Recently, nano-drug delivery system has been experiencing main interest as a new approach for targeting therapeutic agents to the target sites in a controlled, sustained manner and has various advantages as compared to the conventional drug delivery system like, increased solubility, bioavailability, improved pharmacokinetic profile of drugs, surface area and rate of dissolution and additionally, overcomes the problems related to hydrophobicity, toxicity. Present review summarized the intervention of nanotechnology to overcome the limitations/ risk associated with current anti-inflammatory drugs of different classes.

Nintedanib is a competitive inhibitor of non-receptor tyrosine kinase (nRTKs) and receptor tyrosine kinase (RTKs). Nintedanib is a substrate for the P-glycoprotein transporter, which returns ingested substances to the gastrointestinal lumen. At present, Nintedanib is being prescribed for individuals diagnosed with idiopathic pulmonary fibrosis (IPF). This assessment provides a concise overview of the latest patents pertaining to Nintedanib. The patents covered in this analysis are categorized into sections, including patents related to the active ingredient, polymorph, formulation, and treatment method. The purpose of this compilation is to offer researchers convenient access to all the relevant patents in a single resource. Information was collected from diverse web databases, including both paid and free sources. Paid databases, such as Orbit® and SciFinder® were utilized as examples. On the other hand, free databases, such as the European Patent Office's Espacenet®, WIPO Patentscope® the Indian patent database, and Google Patents, were also accessed for data gathering purposes. The orange-book listed patents for Nintedanib are set to expire in July 2029. These patents explore various excipients to address the solubility issue in the long-term storage of the formulation. However, despite these efforts, there is still a need for further research to enhance the properties of the Nintedanib formulation. Extensive research has been conducted on multiple methods for manufacturing Nintedanib and its formulations. This dynamic study has the potential to create opportunities for numerous generic companies to enter the United States market. This, in turn, will improve healthcare accessibility by lowering costs.