Natural substance geraniol has anti-inflammatory and antioxidant qualities. It may be used to treat metabolic diseases such as diabetes, obesity, and cardiovascular illnesses. Innovations in nanoformulations enhance geraniol's absorption, stability, and targeted distribution, augmenting its therapeutic effectiveness and mitigating side effects, despite the limits of traditional treatment.

As of the 7 of July 2024, 775,754,322 confirmed cases of COVID-19, including 7,053,902 deaths worldwide, had been reported to the WHO (World Health Organization). Nevertheless, untill the 15 of July 2024, a total of 13,578,710,228 vaccine doses had been administered, with almost no country spared from COVID-19 attacks. The pathophysiology of this virus is complicated, and several symptoms require a deep understanding of the actual mechanisms. It is unclear why some patients develop severe symptoms while others do not, although literature suggests a role for vitamin D. Vitamin D plays a crucial role in the infection or in ameliorating the severity of symptoms. The mechanism of action of vitamin D and vitamin D deficiency (VDD) is well understood. VDD is associated with increased hospitalization of severely ill patients and increased levels of COVID-19-caused mortality. Recent studies suggest that vitamin D levels and genetic variations in the vitamin D receptor (VDR) gene significantly impact the severity and outcomes of COVID-19, especially in the infections caused by Delta and Omicron variants. Furthermore, VDD causes immune system dysregulation upon infection with SARS-CoV-2, indicating that vitamin D sufficiency is crucial in fighting against COVID-19 infection. The therapeutic effect of vitamin D raises interest in its potential role as a prophylactic and treatment adjunct. We evaluate the immunomodulatory effects of vitamin D and its ability to enhance the efficacy of new antiviral drugs like molnupiravir and paxlovid against SARS-CoV-2. This review discusses the role of vitamin D sufficiency and VDD in COVID-19 initiation and progression, emphasizing the molecular mechanisms by which vitamin D exerts its actions as a proactive step for the next pandemic. However, there is still no clear evidence of vitamin D's impact on prevention and treatment, leading to contradictory findings. Therefore, large-scale randomized trials are required to reach a definitive conclusion. A bibliometric analysis of publications related to vitamin D, immunity, and COVID-19 revealed a significant increase in research activity in this area, particularly in 2020-2024, underscoring the growing recognition of vitamin D's potential role in the context of the pandemic.

The discovery of nitric oxide's role in biological processes like platelet function, vasodilation, cell permeability, and inflammation has advanced our understanding of organic nitrate therapy's hemodynamic and nonhemodynamic effects. Short-term use of organic nitrates prevents left ventricular enlargement and infarct expansion. However, information on their long-term impact on LV remodeling in post-acute cardiac dysfunction patients is limited. In this study, we utilized an innovative active hydrogel with gelatin (Gel)/polyethylene glycol (PEG)/polylactic acid (PLA) encapsulating gold nanoparticles (AuNPs)-based drug delivery system for the sustained release of nitroglycerin (NTG). Gel/PEG/PLA/NTG/AuNPs hydrogel-based system is a non-transplant surgical method that can adhere to the surface of the heart and deliver the drug directly to the epicardium. Cardiac dysfunction was induced by ligating the left anterior descending coronary artery. Echocardiograms were used to study the pre- and post-operative hemodynamics. Hematoxylin and eosin (H&E) and Masson's trichrome stain (MTS) staining revealed that the acute myocardial infarction (AMI) rats' group had irregularly shaped fibers and a lack of transverse striations, whereas Gel/PEG/PLA/NTG/AuNPs hydrogel group showed significant improvement. Rats in the Gel/PEG/PLA hydrogel group demonstrated marked vasodilation, compared to the AMI group. Mechanistically, we determined that hydrogel disrupts the initiation of post-cardiac dysfunction via inhibiting Wnt/β-catenin transcriptional activation. Hence, the Gel/PEG/PLA/NTG/AuNPs hydrogel group effectively protected against ischemic injury and inflammation in AMI, demonstrating a novel method for treating acute cardiac dysfunction.

There is a growing body of evidence indicating the significant role of the immune system and immune cells in the progression of Alzheimer's disease (AD). However, the exact role of genes from various immune cell types in AD remains unclear. We aimed to utilize summary data-based Mendelian randomization (SMR) to explore the potential causal relationships between genes in specific immune cells and the risk of AD.

Postoperative pain management is one of the most challenging treatments after orthopaedic surgery, and improved medical treatment options are urgently needed. This study aimed to evaluate the efficacy and safety of 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1, 2-benzothiazin-3-carboxamide 1,1-dioxide (QP001) for moderate to severe pain following orthopaedic surgery.

The increased production of reactive oxygen species (ROS) by human neutrophils can lead to oxidative imbalances and several diseases, such as inflammatory bowel disease (IBD). Opuntia ficus-indica (O. ficus-indica) is rich in bioactive substances with anti-inflammatory properties. This study aimed to identify the bioactive compounds present in aqueous cladodes extract (ACE) of O. ficus-indica using high-performance liquid chromatography (HPLC) and to test its effects on human neutrophil inflammatory functions and on ulcerative colitis (UC) induced by acetic acid (Aa) in rats. ROS production and degranulation by neutrophils were assessed by luminol-amplified chemiluminescence, enzymatic techniques, and western blotting. In vivo, the experiment involved seven groups of rats: a negative control group (NaCl), the acetic acid group (Aa), and groups treated with oral sulfasalazine (150 mg/kg) or various doses of ACE for 7 days. Colonic lesions were induced by an intra-rectal Aa injection, and inflammation was assessed. HPLC analysis identified gallic acid, catechin, caffeic acid, and ferulic acid as major compounds in ACE. In vitro, ACE inhibited neutrophil ROS production, including superoxide anion produced by NADPH oxidase, and significantly reduced myeloperoxidase activity and neutrophil degranulation. In vivo, ACE protected rats from Aa-induced histopathological damage of the colonic mucosa, significantly increased catalase, superoxide dismutase and reduced glutathione levels, and significantly suppressed the increases of plasma cytokines (TNF-α and IL-1β) observed in the Aa group. In conclusion, O. ficus-indica ACE has significant anti-inflammatory properties by restoring oxidative balance, indicating that it could be a potential source of therapeutic agents for inflammatory diseases, particularly UC.

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.

Nucleocytoplasmic translocation of HMGB1 (high mobility group box-1) plays a significant role in disease progression. Several methods contribute to the translocation of HMGB1 from the nucleus to the cytoplasm, including inflammasome activation, TNF-α signaling, CRM1-mediated transport, reactive oxygen species (ROS), JAK/STAT pathway, RIP3-mediated p53 involvement, XPO-1-mediated transport, and calcium-dependent mechanisms. Due to its diverse functions at various subcellular locations, HMGB1 has been identified as a crucial factor in several Central Nervous System (CNS) disorders, including Huntington's disease (HD), Parkinson's disease (PD), and Alzheimer's disease (AD). HMGB1 displays a wide array of roles in the extracellular environment as it interacts with several receptors, including CXCR4, TLR2, TLR4, TLR8, and RAGE, by engaging in these connections, HMGB1 can effectively regulate subsequent signaling pathways, hence exerting an impact on the progression of brain disorders through neuroinflammation. Therefore, focusing on treating neuroinflammation could offer a common therapeutic strategy for several disorders. The objective of the current literature is to demonstrate the pathological role of HMGB1 in various neurological disorders. This review also offers insights into numerous therapeutic targets that promise to advance multiple treatments intended to alleviate brain illnesses.

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, C, 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.

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.

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.

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.

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.

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

Cancer is the predominant and major cause of fatality worldwide, based on the different types of cancer. There is a limitation in the current treatment. So we need better therapeutic agents that counteract the progression and development of malignant tumours. Plant-derived products are closely related and useful for human health. Luteolin is a polyphenolic flavonoid bioactive molecule that is present in various herbs, vegetables, fruits, and flowers and exhibits chemoprotective and pharmacological activity against different malignancies. To offer innovative approaches for the management of various cancers, we present a comprehensive analysis of the latest discoveries on luteolin. The aim is to inspire novel concepts for the development of advanced pharmaceuticals targeting cancer and search specifically targeted reviews and research articles published from January 1999 to January 2024 that investigated the application of luteolin in various cancer management. A thorough literature search utilizing the keywords "luteolin" "Signalling Pathway" "cancer" and nanoparticles was performed in the databases of Google Scholar, Web of Science, SCOPUS, UGC care list and PubMed. Through the compilation of existing research, we have discovered that luteolin possesses several therapeutic actions against various cancer via a signaling pathway involving the of NF-κB regulation, AMPK/mTOR, toll-like receptor, Nrf-2, PI3K/Akt MAPK and Wnt/β-catenin and their underlying mechanism of action has been well understood. This review intended to completely integrate crucial information on natural sources, biosynthesis, pharmacokinetics, signaling pathways, chemoprotective and therapeutic properties against various cancers, and nanoformulation of luteolin.

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.

Neonatal hypoxic-ischaemic encephalopathy (HIE) remains one of the major causes of neonatal death and long-term neurological disability. Due to its complex pathogenesis, there are still many challenges in its treatment. In our previous studies, we found that quercetin can alleviate neurological dysfunction after hypoxic-ischaemic brain injury (HIBI) in neonatal mice. As demonstrated through in vitro experiments, quercetin can inhibit the activation of the TLR4/MyD88/NF-κB signalling pathway and the inflammatory response in the microglial cell line BV2 after oxygen-glucose deprivation. However, the in-depth mechanism still needs to be further elucidated. In the present study, 7 day-old neonatal ICR mice or BV2 cells were treated with quercetin with or without the SIRT1 inhibitor EX527 via neurobehavioural, histopathological and molecular methods. In vivo experiments have shown that quercetin can significantly improve the performance of HI mice in behavioural tests, such as the Morris water maze, rotarod test and pole climbing test, and reduce HI insult-induced structural brain damage, cell apoptosis and hippocampal neuron loss. Quercetin also inhibited the immunofluorescence intensity of the microglial M1 marker CD16 + 32 and significantly downregulated the expression of the M1-related proteins iNOS, IL-1β and TNF-α. Moreover, quercetin increased the immunofluorescence intensity of the microglial M2 marker CD206 and significantly increased the expression of the M2-related proteins Arg-1 and IL-10. In addition, quercetin limits the nucleocytoplasmic translocation and release of microglial HMGB1 and further suppresses the activation of the downstream TLR4/MyD88/NF-κB signalling pathway. The above effects of quercetin are partially weakened by pretreatment with EX527. Similar results were found in in vitro experiments, and the mechanism further revealed that the rebalancing effect of quercetin on microglial polarization is achieved through the SIRT1-mediated reduction in HMGB1 acetylation levels. This study provides new and complementary insights into the neuroprotective effects of quercetin and a new direction for the treatment of neonatal HIE.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, severe, and potentially life-threatening skin and mucous membrane disorders. They are characterized by widespread skin and mucosal detachment and necrosis, and are classified based on the percentage of total body surface area (TBSA) affected. Given the severe and often life-threatening nature of these conditions, the identification and implementation of effective treatments is crucial. Notably, cyclosporin has demonstrated efficacy in managing these challenging conditions.

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.

Hypoxia-inducible factor 1α (HIF-1α) is a crucial transcription factor that regulates cellular responses to low oxygen levels (hypoxia). In Alzheimer's disease (AD), emerging evidence suggests a significant involvement of HIF-1α in disease pathogenesis. AD is characterized by the accumulation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs), leading to neuronal dysfunction and cognitive decline. HIF-1α is implicated in AD through its multifaceted roles in various cellular processes. Firstly, in response to hypoxia, HIF-1α promotes the expression of genes involved in angiogenesis, which is crucial for maintaining cerebral blood flow and oxygen delivery to the brain. However, in the context of AD, dysregulated HIF-1α activation may exacerbate cerebral hypoperfusion, contributing to neuronal damage. Moreover, HIF-1α is implicated in the regulation of Aβ metabolism. It can influence the production and clearance of Aβ peptides, potentially modulating their accumulation and toxicity in the brain. Additionally, HIF-1α activation has been linked to neuroinflammation, a key feature of AD pathology. It can promote the expression of pro-inflammatory cytokines and exacerbate neuronal damage. Furthermore, HIF-1α may play a role in synaptic plasticity and neuronal survival, which are impaired in AD. Dysregulated HIF-1α signaling could disrupt these processes, contributing to cognitive decline and neurodegeneration. Overall, the involvement of HIF-1α in various aspects of AD pathophysiology highlights its potential as a therapeutic target. Modulating HIF-1α activity could offer novel strategies for mitigating neurodegeneration and preserving cognitive function in AD patients. However, further research is needed to elucidate the precise mechanisms underlying HIF-1α dysregulation in AD and to develop targeted interventions.