Inflammopharmacology最新文献

Background: We aimed to examine the efficacy of intravenous vitamin C (IV-VC) in the treatment of hospitalized patients with moderate or severe COVID-19.

Method: We conducted a single-center and retrospective study including patients with COVID-19 diagnosis who were hospitalized. Patients were categorized into three groups as those who received low-dose (LDVC group, 2 g/day, n = 183) or high-dose IV-VC (HDVC group, 25 g/day, n = 41) and who did not receive IV-VC (control group, n = 46).

Results: 270 patients aged 19-97 years were enrolled. The median length of stay (LOS) was significantly high (9 days) in patients treated with high-dose VC when compared to patients treated with low-dose VC and control patients (6 vs 5 days, respectively). Need for intensive care unit (ICU) transfer was found to be significantly low in patients treated with low-dose VC (25.7%); contrarily, control patients had significantly higher rates of ICU transfer (67.4%), when compared to patients treated with high-dose VC (39%). Mortality of the LDVC group was significantly lower than that of the HDVC group (11.5 vs 29.3%). However, mortality rates were similar between the control and HDVC groups (21.7 vs 29.3%). According to the multivariate stepwise logistic regression mortality analysis, percent of change (∆%)-BUN was the most significant variable (p < 0.001), the second significant variable was ∆%-AST (p = 0.002), the third significant variable was respiratory distress (p = 0.002), and the fourth significant variable was the IV-VC groups (p = 0.017). The mortality risk of those in the LDVC group was 10.2 times low compared to the control group. Similarly, the risk of mortality in the HDVC group was 6.5 times lower than that of the control group.

Conclusion: Especially low and continious doses of IV-VC suggest fewer days of in-hospital LOS and survival benefit in hospitalized patients with moderate and severe COVID-19. Logistic regression analysis revealed that high-dose VC supplementation also had a mortality-reducing effect.

Pseudomonas aeruginosa is a repertoire of several virulence factors that create a frightening high pathogenicity level as well as high antimicrobial resistance toward commercially used antibiotics. Therefore, finding a new alternative to traditional antimicrobials is a must. Resveratrol is a very famous phytochemical that harbors many beneficial health properties by possessing antibacterial, anti-inflammatory, and antioxidant properties. The current study aimed to explore the antimicrobial efficacy of resveratrol against P. aeruginosa and explore its ability to accelerate wound healing in a murine model. The obtained results revealed the potent antimicrobial, antivirulence, and wound-healing accelerating potentials of resveratrol against carbapenem-resistant P. aeruginosa (CRPA)-septic wounds. It significantly lowered the transcript levels of P. aeruginosa virulent genes toxA, pelA, and lasB. Additionally, resveratrol significantly accelerated skin wound healing by shortening the inflammatory phase and promoting re-vascularization, cell proliferation, re-epithelialization, and collagen deposition. Furthermore, it increased the immunoexpression of αSMA along with a reduction of the mRNA levels of VEGF, IL-1β, and TNF-α genes. Resveratrol has high therapeutic potential for the treatment of P. aeruginosa wound infection and is a prospective and promising candidate for this problem.

Eucalyptus essential oils (EEOs) have gained significant attention recently anticipated to their broad range of prospective benefits in various biological applications. They have been proven to have strong antibacterial properties against a variety of bacteria, fungi, and viruses. This makes them valuable in combating infections and supporting overall hygiene. The active compounds present in these oils can help alleviate inflammation, making them valuable in addressing inflammatory conditions such as arthritis, respiratory ailments, and skin disorders. Respiratory health benefits are another prominent aspect of EEOs. Inhalation of these oils can help promote clear airways, relieve congestion, and ease symptoms of respiratory conditions like coughs, colds, and sinusitis. They are often utilized in inhalation therapies and chest rubs. They can be used topically or in massage oils to alleviate muscle and joint pain. Furthermore, these oils have shown potential in supporting wound healing. Their antimicrobial activity helps prevent infection, while their anti-inflammatory and analgesic properties contribute to reducing inflammation and pain associated with wounds. In aromatherapy, EEOs are renowned for their invigorating and uplifting qualities, promoting mental clarity, relaxation, and stress relief. Overall, EEOs hold great promise in biological applications, offering a natural and versatile approach to promote health and well-being. Continued research and exploration of their therapeutic potential will further unveil their benefits and broaden their applications in various fields.

Acute pancreatitis is a potentially life-threatening inflammatory disorder of the exocrine pancreas characterized by early activation of pancreatic enzymes followed by macrophage-driven inflammation, and pancreatic acinar cell death. The most common causes are gallstones and excessive alcohol consumption. Inflammation and oxidative stress play critical roles in its pathogenesis. Despite increasing incidence, currently, no specific drug therapy is available to treat or prevent acute pancreatitis, in particular severe acute pancreatitis. New therapeutic agents are very much needed. Plant polyphenols have attracted extensive attention in the field of acute pancreatitis due to their diverse pharmacological properties. In this review, we discuss the potential of plant polyphenols in inhibiting the occurrence and development of acute pancreatitis via modulation of inflammation, oxidative stress, calcium overload, autophagy, and apoptosis, based on the currently available in vitro, in vivo animal and very few clinical human studies. We also outline the opportunities and challenges in the clinical translation of plant polyphenols for the treatment of the disease. We concluded that plant polyphenols have a potential therapeutic effect in the management and treatment of acute pancreatitis. Knowledge gained from this review will hopefully inspire new research ideas and directions for the development and application of plant polyphenols for treating this disease.

Background: Osteoarthritis (OA) is a common age-related disease that causes pain and impaired mobility. Various blood metabolites are reportedly associated with bone health; however, their impact on OA remains unclear. Therefore, we conducted a metabolome-wide Mendelian randomization (MR) study to identify causal metabolites and therapeutic targets in OA.

Methods: Genetic associations of metabolites were derived from the largest genome-wide association study (GWAS) of the blood metabolome, which provided summary-level data on 1091 blood metabolites. Genetic associations with OA were obtained from four large-scale GWAS: McDonald's study (140,025 cases, 344,349 controls), Zengini's study (12,658 cases, 50,898 controls), Dönertaş's study (39,515 cases, 445,083 controls), and Tachmazidou's study (39,427 cases, 378,169 controls). MR and colocalization analyses were performed to validate the causal roles of the candidate metabolites. Further analyses were conducted using expression quantitative trait locus-based MR, single-cell sequencing data, protein-protein interaction networks, and druggability assessments. These analyses aimed to identify the differentially expressed genes and prioritize them as potential therapeutic targets.

Results: The genetically predicted levels of 10 metabolites were associated with OA. Elevated levels of five metabolites and reduced levels of another five metabolites were associated with an increased OA risk. Among these, five metabolites were prioritized based on the most compelling evidence. Seven genes were identified as potentially involved and could serve as novel therapeutic targets for OA.

Conclusion: Several blood metabolites were associated with OA, providing new insights into the etiology of OA and highlighting promising therapeutic targets.

Thiostrepton (TST) is a naturally occurring oligopeptide antibiotic with a demonstrated capacity to antagonize a broad spectrum of Gram-positive bacteria. It has been utilized as a safe antimicrobial agent in veterinary medicine. Despite its therapeutic potential, the clinical application of TST has been constrained by its poor solubility and bioavailability. However, an increasing number of studies indicate that TST possesses diverse pharmacological activities, including its significant role in microbe resistance and cancer countering. Notably, recent studies have pointed out that TST also possesses anti-inflammatory potential. It has exhibited promising therapeutic efficacy across various in vivo and in vitro disease models, including non-alcoholic fatty liver disease, inflammatory bowel disease, sepsis, psoriasis-like inflammation, and periodontitis. In this review, we describe the various pharmacological activities of TST, particularly its anti-inflammatory activity demonstrated in a variety of inflammatory diseases and the underlying mechanisms. These effects highlight the potential of TST as an anti-inflammatory agent for the treatment of inflammation diseases and for enhancing cellular therapies.

The intricate Gut microbiome is evolving as an important system and is hypothesized to be a "metabolic organ" within the host. Alterations in Gut microbiota and inflammation associated with several diseases play a crucial role in drug transformation through microbiota-host co-metabolism, modified pharmacokinetic and pharmacodynamics profiles, and may result in the formation of toxic metabolites with interference in drug response. In recent studies, a large number of drugs are reported that are co-metabolized by the host and the Gut microbial enzymes. we summarize the direct and indirect involvement of Gut microbiome promotion or inhibition of cardiovascular diseases, mechanisms on bioavailability, and therapeutic outcomes of cardiovascular drugs, particularly pharmacokinetics and pharmacodynamics profiles in light of AUC, T_max, C_max, and bioavailability and drug transportation via immune cells, inter-individual variations in intestinal microbial taxonomy, influence of drugs on diversity and richness of microflora, high lightening limitations and significance of in personalized medicine. Recent advances in target-drug delivery by nanoparticles with limitations and challenges in application are discussed. The cross-talk between Gut microbiota and cardiovascular drugs signifies a better understanding and rationale for targeting the Gut microbiota to improve the therapeutic outcome for cardiovascular diseases, with present-day limitations.

Myocardial ischemia, resulting from coronary artery blockage, precipitates cardiac arrhythmias, myocardial structural changes, and heart failure. The pathophysiology of MI is mainly based on inflammation and cell death, which are essential in aggravating myocardial ischemia and reperfusion injury. Emerging research highlights the functionality of high mobility group box-1, a non-histone nucleoprotein functioning as a chromosomal stabilizer and inflammatory mediator. HMGB1's release into the extracellular compartment during ischemia acts as damage-associated molecular pattern, triggering immune reaction by pattern recognition receptors and exacerbating tissue inflammation. Its involvement in signaling pathways like PI3K/Akt, TLR4/NF-κB, and RAGE/HMGB1 underscores its significance in promoting angiogenesis, apoptosis, and reducing inflammation, which is crucial for MI treatment strategies. This review highlights the complex function of HMGB1 in the pathogenesis of myocardial infarction by summarizing novel findings on the protein in ischemic situations. Understanding the mechanisms underlying HMGB1 could widen the way to specific treatments that minimize the severity of MI and enhance patient outcomes.

Background: Montanoa grandiflora, a plant species native from Mexico to Central America, locally known as "Teresita" in Yucatán, México, is used to alleviate anxiety, rheumatism, and stomach issues. This study aims to investigate the anti-inflammatory properties of the methanol extract of Montanoa grandiflora leaves (MMG) in experimental models of inflammation.

Methods: Gas chromatography-mass spectroscopy was used to characterize the MMG; cytotoxicity was assessed by MTT assay on murine macrophages and hemolysis assay. The in vitro anti-inflammatory activity was evaluated on LPS-stimulated murine macrophages by measuring of pro- and anti-inflammatory cytokines, NO and H₂O₂ release. The in vivo anti-inflammatory activity was evaluated using carrageenan-induced mouse paw edema, 12-O-tetradecanoylphorbol 13-acetate induced-ear edema, and 1-fluoro-2,4-dinitrobenzene induced-delayed-type hypersensitivity. In addition, the serum levels of prostaglandins and leukotrienes were assessed.

Results: The main compounds found in MMG were terpenes (i.e., β-caryophyllene, (-)-α-cubebene, alloaromadendrene, ( +)-δ-cadinene, β-eudesmol), alkaloid (( ±)-nor-β-hydrastine), cyclic polyol (quinic acid), carbohydrates and their derivatives, and fatty acids (octadecatrienoic acid and octadecanoic acid). MMG did not exhibit cytotoxic or hemolytic activity. However, it demonstrated in vitro anti-inflammatory effects by increasing the production of IL-10, decreasing the levels of TNF-α, IL-1β, IL-6, NO and H₂O₂. MMG significantly reduced carrageenan-induced paw edema, TPA-induced ear edema, and DNFB-induced delayed-type hypersensitivity in mice with effects comparable to those of standard drugs, as well as serum levels of prostaglandins and leukotrienes.

Conclusion: The anti-inflammatory activity of MMG is associated with increased IL-10 levels and inhibiting inflammatory cell migration mechanisms, without causing cytotoxic or hemolytic damage in both in vitro and in vivo assays.