Role and uptake of metal-based nanoconstructs as targeted therapeutic carriers for rheumatoid arthritis.

Rheumatoid Arthritis (RA) is a chronic autoimmune systemic inflammatory disease that affects the joints and other vital organs and diminishes the quality of life. The current developments and innovative treatment options have significantly slowed disease progression and improved their quality of life. Medicaments can be delivered to the inflamed synovium via nanoparticle systems, minimizing systemic and undesirable side effects. Numerous nanoparticles such as polymeric, liposomal, and metallic nanoparticles reported are impending as a good carrier with therapeutic properties. Other issues to be considered along are nontoxicity, nanosize, charge, optical property, and ease of high surface functionalization that make them suitable carriers for drug delivery. Metallic nanoparticles (MNPs) (such as silver, gold, zinc, iron, titanium oxide, and selenium) not only act as good carrier with desired optical property, and high surface modification ability but also have their own therapeutical potential such as anti-oxidant, anti-inflammatory, and anti-arthritic properties, making them one of the most promising options for RA treatment. Regardless, cellular uptake of MNPs is one of the most significant criterions for targeting the medication. This paper discusses the numerous interactions of nanoparticles with cells, as well as cellular uptake of NPs. This review provides the mechanistic overview on MNPs involved in RA therapies and regulation anti-arthritis response such as ability to reduce oxidative stress, suppressing the release of proinflammatory cytokines and expression of LPS induced COX-2, and modulation of MAPK and PI3K pathways in Kuppfer cells and hepatic stellate cells. Despite of that MNPs have also ability to regulates enzymes like glutathione peroxidases (GPxs), thioredoxin reductases (TrxRs) and act as an anti-inflammatory agent.

HIV1-Nef perturbs the integrity of blood testis barrier in rat model.

The blood-testis barrier is a specialized feature within the mammalian testis, located in close proximity to the basement membrane of seminiferous tubules. This barrier serves to divide the seminiferous epithelium into distinct basal and adluminal (apical) compartments. The selectivity of the BTB to foreign particles makes it a safe haven for the virus, and the high affinity of HIV for testis might lead to the vertical transmission of the virus. In the present study, recombinant HIV1-Nef (rNef) protein was injected intravenously to examine the effect of rNef on BTB. SD male rats received 250 µg and 500 µg of rNef along with 2% Evans blue dye within 1 ml through the tail vein. After 1 hour of perfusion, the animals were sacrificed for analysis. The dye migration assay and ELISA confirmed a significant impairment in the blood-testis barrier (BTB) and the manifestation of rNef in testes tissues, respectively. Moreover, a decline in the expression of tight junction proteins, including ZO1 and Occludin, was observed during rNef-induced BTB disruption. Overall, our findings demonstrated that rNef induces BTB disruption through various signaling events. At the site of ectoplasmic specialization of the seminiferous epithelium, the localization of cadherins was found to be disrupted, making the testis a vulnerable site. In conclusion, rNef perturbs the integrity of the blood-testis barrier in rat models; hence, it can also serve as a suitable model for studying the dynamics of the blood-testis barrier.

Established a rodent model to study the integrity of the blood testis barrier (BTB).Recombinant Nef (rNef) of HIV1 can breach the toughest physiological barrier of BTB.Integrity of BTB gets interrupted by rNef through the 'disengagement' and 'engagement' mechanisms of BTB dynamics.Major constituent proteins of BTB, including Occludin and ZO-1 were found to be highly disrupted by rNef; and seem to be the key aberrant for the compromised BTB.rNef also dislocated the localization of N & E cadherins in the rat testes; which would have affected the cadherin-based epithelial adhesion system of BTB and finally caused the breach.

Menopausal hormone therapy and breast cancer risk: a population-based cohort study of 1.3 million women in Norway.

BACKGROUND: It is important to monitor the association between menopausal hormone therapy (HT) use and breast cancer (BC) risk with contemporary estimates, and specifically focus on HT types and new drugs. METHODS: We estimated hazard ratios (HR) of BC risk according to HT type, administration route and individual drugs, overall and stratified by body mass index (BMI), molecular subtype and detection mode, with non-HT use as reference. RESULTS: We included 1,275,783 women, 45+ years, followed from 2004, for a median of 12.7 years. Oral oestrogen combined with daily progestin was associated with the highest risk of BC (HR 2.42, 95% confidence interval (CI) 2.31-2.54), with drug-specific HRs ranging from Cliovelle®: 1.63 (95% CI 1.35-1.96) to Kliogest®: 2.67 (2.37-3.00). Vaginal oestradiol was not associated with BC risk. HT use was more strongly associated with luminal A cancer (HR 1.97, 95% CI 1.86-2.09) than other molecular subtypes, and more strongly with interval (HR 2.00, 95% CI: 1.83-2.30) than screen-detected (HR 1.33, 95% CI 1.26-1.41) BC in women 50-71 years. HRs for HT use decreased with increasing BMI. CONCLUSIONS: The use of oral and transdermal HT was associated with an increased risk of BC. The associations varied according to HT type, individual drugs, molecular subtype, detection mode and BMI.

Global status, recent trends, and knowledge mapping of olive oil research and cardiovascular disease: 50 years of investigations through bibliometric analysis.

In the Mediterranean diet, olive oil serves as the predominant fat source and has been linked to a decreased risk of mortality related to cardiovascular diseases (CVD). Still, there is no conclusive evidence correlating olive oil consumption to CVD. The aim of this study is to assess the global research, current research trends, and knowledge mapping related to the correlation between the consumption of olive oil and CVD using bibliometric analysis. On August 19, 2023, a title-specific literature search was conducted on the Scopus database using the search terms "olive oil" and "cardiovascular disease" with a date range of the past 50 years. Subsequently, bibliometric tools such as VOSviewer and Bibliometrix were employed to analyze and evaluate the obtained documents. The search yielded (n = 429) publications and showed an upward trend in the annual publication count over the last five decades. The publication number exhibited a gradual increase with a rate of 5.55%. The results also indicated that 2530 authors, 759 institutions, 47 countries, and 223 journals have publications in this research domain. The present bibliometric study will be a valuable research reference for describing the worldwide research patterns concerning the relationship between olive oil and CVD during the past 50 years. In the future, the application of olive oil for the treatment of CVDs may be an emerging research trend. Apart from this, collaborations among authors, countries, and organizations are expected.

Targeting Pathways and Integrated Approaches to Treat Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic symmetrical systemic disorder that not only affects joints but also other organs such as heart, lungs, kidney, and liver. Approximately there is 0.5%-1% of the total population affected by RA. RA pathogenesis still remains unclear due to which its appropriate treatment is a challenge. Further, multitudes of factors have been reported to affect its progression i.e. genetic factor, environmental factor, immune factor, and oxidative factor. Therapeutic approaches available for the treatment of RA include NSAIDs, DMARDs, enzymatic, hormonal, and gene therapies. But most of them provide the symptomatic relief without treating the core of the disease. This makes it obligatory to explore and reach the molecular targets for cure and long-term relief from RA. Herein, we attempt to provide extensive overlay of the new targets for RA treatment such as signaling pathways, proteins, and receptors affecting the progression of the disease and its severity. Precise modification in these targets such as suppressing the notch signaling pathway, SIRT 3 protein, Sphingosine-1-phosphate receptor and stimulating the neuronal signals particularly efferent vagus nerve and SIRT 1 protein may offer long term relief and potentially diminish the chronicity. To target or alter the novel molecules and signaling pathway a specific delivery system is required such as liposome, nanoparticles and micelles and many more. Present review paper discusses in detail about novel targets and delivery systems for treating RA.

Plant-Based Approaches for Rheumatoid Arthritis Regulation: Mechanistic Insights on Pathogenesis, Molecular Pathways, and Delivery Systems.

Rheumatoid arthritis (RA) is classified as a chronic inflammatory autoimmune disorder, associated with a varied range of immunological changes, synovial hyperplasia, cartilage destructions, as well as bone erosion. The infiltration of immune-modulatory cells and excessive release of proinflammatory chemokines, cytokines, and growth factors into the inflamed regions are key molecules involved in the progression of RA. Even though many conventional drugs are suggested by a medical practitioner such as DMARDs, NSAIDs, glucocorticoids, etc., to treat RA, but have allied with various side effects. Thus, alternative therapeutics in the form of herbal therapy or phytomedicine has been increasingly explored for this inflammatory disorder of joints. Herbal interventions contribute substantial therapeutic benefits including accessibility, less or no toxicity and affordability. But the major challenge with these natural actives is the need of a tailored approach for treating inflamed tissues by delivering these bioactive agentsat an appropriate dose within the treatment regimen for an extended periodof time. Drug incorporated with wide range of delivery systems such as liposomes, nanoparticles, polymeric micelles, and other nano-vehicles have been developed to achieve this goal. Thus, inclinations of modern treatment are persuaded on the way to herbal therapy or phytomedicines in combination with novel carriers is an alternative approach with less adverse effects. The present review further summarizes the significanceof use of phytocompounds, their target molecules/pathways and, toxicity and challenges associated with phytomolecule-based nanoformulations.

Technical Considerations, Applications, and Benefits of Organogels in Topical Drug Delivery Systems.

Organogels represent semi-solid systems where an organic liquid phase is entrapped within a three-dimensional network formed by self-assembled, crosslinked, or entangled gelator fibers. These versatile materials find applications in a wide range of fields, including chemistry, pharmaceuticals, cosmetics, biotechnology, and food technology. Notably, in pharmacology, they serve as valuable platforms for drug and vaccine delivery, facilitating the transport of active ingredients through various routes such as transdermal, oral, and parenteral. However, their previous utility as drug delivery systems was hindered by the toxicity associated with the organic solvents used. The pharmacokinetics of medications delivered via organogels are primarily influenced by the distinctive properties of these materials, specifically their "high permeability and poor aqueous solubility," which can impact the bioavailability of the drugs. Organogels can be employed topically or for the controlled release of medications through cutaneous administration and percutaneous absorption, expanding their scope of application beyond conventional drug delivery methods. Organogels hold significant promise as drug delivery vehicles due to their biocompatibility, non-irritating properties, and thermoremanent characteristics. They enable the formulation of diverse drug delivery systems by incorporating both hydrophilic and hydrophobic bioactive compounds within the gel matrix. This comprehensive review offers an overview of organogels, encompassing their nature, synthesis, characterization, and properties. Special attention is directed towards cutting-edge technologies employed in designing organogels as potential controlled delivery systems, with a focus on their emerging therapeutic applications.

A Review on Molecular Docking As an Interpretative Tool for Molecular Targets in Disease Management.

One of the most often utilized methods for drug discovery is molecular docking. With docking, one may discover new therapeutically relevant molecules by targeting the molecule and predicting the target-ligand interactions as well as different conformation of ligand at various positions. The prediction signifies the effectiveness of the molecule or the developed molecule having different affinity with target. Drug discovery plays an important role in the development of a new drug molecule of different moiety attached to it, which leads us in the management of several diseases. In silico approach led us to identification of numerous diseases caused by virus, fungi, bacteria, protozoa, and other microorganisms that affect human health. By means of computational approach, we can categorize disease symptoms and use the drugs available for such types of warning signs. After the docking process, molecular dynamics computational technique helps in the simulation of the physical movement of atoms and molecules for a fixed period of time, giving a view of the dynamic evaluation of the system. This review is an attempt to illustrate the role of molecular docking in drug development.

Mechanistic insight on the role of iRhom2-TNF-α-BAFF signaling pathway in various autoimmune disorders.

iRhom2 is a crucial cofactor involved in upregulation of TNF receptors (TNFRs) and the pro-inflammatory cytokine tumor necrosis factor (TNF-) from the cell surface by ADAM17. Tumor necrosis factor- α converting enzyme (TACE) is another name given to ADAM17. Many membrane attached biologically active molecules are cleaved by this enzyme which includes TNFRs and the pro-inflammatory cytokine tumor necrosis factor- α. The TNF receptors are of two types TNFR1 and TNFR2. iRhom2 belongs to the pseudo-protease class of rhomboid family, its abundance is observed in the immune cells. Biological activity of ADAM17 is affected in multiple levels by the iRhom2. ADAM17 is trafficked into the Golgi apparatus by the action of iRhom2, where it gets matured proteolytically and is stimulated to perform its function on the cell surface. This process of activation of ADAM17 results in the protection of the organism from the cascade of inflammatory reactions, as this activation blocks the TNF- α mediated secretion responsible for inflammatory responses produced. Present paper illustrates about the iRhom2-TNF-α-BAFF signaling pathway and its correlation with several autoimmune disorders such as Rheumatoid Arthritis, Systemic Lupus Erythematosus, Hemophilia Arthropathy, Alzheimer's disease and Tylosis with esophageal cancer etc.

Genetic newborn screening and digital technologies: A project protocol based on a dual approach to shorten the rare diseases diagnostic path in Europe.

Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations. It focuses on genetic newborn screening and artificial intelligence-based tools which will be applied to a large European population of about 25.000 infants. The neonatal screening strategy will be based on targeted sequencing, while whole genome sequencing will be offered to all enrolled infants who may show early symptoms but have resulted negative at the targeted sequencing-based newborn screening. We will leverage artificial intelligence-based algorithms to identify patients using Electronic Health Records (EHR) and to build a repository "symptom checkers" for patients and healthcare providers. S4C will design an equitable, ethical, and sustainable framework for genetic newborn screening and new digital tools, corroborated by a large workout where legal, ethical, and social complexities will be addressed with the intent of making the framework highly and flexibly translatable into the diverse European health systems.

Mechanistic prospective and pharmacological attributes of quercetin in attenuation of different types of arthritis.

Arthritis is a frequent autoimmune disease with undefined etiology and pathogenesis. Scientific community constantly fascinating quercetin (QUR), as it is the best-known flavonoid among others for curative and preventive properties against a wide range of diseases. Due to its multifaceted activities, the implementation of QUR against various types of arthritis namely, rheumatoid arthritis (RA), osteoarthritis (OA), gouty arthritis (GA) and psoriotic arthritis (PsA) has greatly increased in recent years. Many research evidenced that QUR regulates a wide range of pathways for instance NF-κB, MAK, Wnt/ß-catenine, Notch, etc., that are majorly associated with the inflammatory mechanisms. Besides, the bioavailability of QUR is a major constrain to its therapeutic potential, and drug delivery techniques have experienced significant development to overcome the problem of its limited application. Hence, this review compiled the cutting-edge experiments on versatile effects of QUR on inflammatory diseases like RA, OA, GA and PsA, sources and bioavailability, therapeutic challenges, pharmacokinetics, clinical studies as well as toxicological impacts. The use of QUR in a health context would offer a tearing and potential therapeutic method, supporting the advancement of public health, particularly, of arthritic patients worldwide.

Corrigendum to "Tanshinone-I for the treatment of uterine fibroids: Molecular docking, simulation, and density functional theory investigations" [Saudi Pharm. J. 31(6) (2023) 1061-1067].

[This corrects the article DOI: 10.1016/j.jsps.2023.05.002.].

Role of vascular endothelial growth factor in tuberculous meningitis: A prospective study from a tertiary care center in North India.

INTRODUCTION: The status of vascular endothelial-derived growth factor (VEGF) in the pathogenesis of tuberculous meningitis (TBM) remains far from clear. We prospectively evaluated the role of serum and cerebrospinal fluid (CSF) VEGF in TBM. PATIENTS AND METHODS: This prospective study was conducted at a tertiary care center in North India from January 2018 to June 2019. Consecutive drug-naive patients (n = 82) of TBM diagnosed on the basis of modified Ahuja's criteria were included in the study. The results were compared with 49 control subjects (n = 49). Serum and CSF VEGF were done in all the cases and controls. Follow-up serum VEGF levels were done in 34 patients after 3 months of completion of antitubercular therapy. The VEGF levels were estimated using the human VEGF enzyme-linked immunosorbent assay kit. RESULTS: The mean age was 29.9 ± 13.1 years. The study group consisted of 33 (40.2%) men and 49 (59.8%) women. BACTEC MGIT960 was positive in 15 (18%) patients while multiplex tuberculosis polymerase chain reaction was positive in 73 (89%) patients. Levels of VEGF in serum and CSF of TBM patients were not elevated when compared to controls. There was no association between final outcome in TBM and decrease in serum levels of VEGF at follow-up. CONCLUSION: VEGF may not be playing a significant role in the pathogenesis of TBM. Future studies with larger sample size may clarify the status of VEGF further in TBM.

Impact of inverted internal limiting membrane-flap technique on functional outcome and structural restoration of small and medium size macular holes.

Purpose: To evaluate the impact of the inverted internal limiting membrane (ILM)-flap technique on the visual outcome and anatomical recovery for small (<250 µ), medium (<400 µ), and large (>400 µ) macular holes (MHs). Methods: Retrospective study included consecutive idiopathic MH cases operated on using the inverted ILM-flap technique. Clinical data were retrieved from electronic medical records (EMRs), surgical videos, and optical coherence tomography (OCT) machines. Eyes with axial length >25 mm, coexisting macular diseases, and follow-up <6 weeks were excluded. Data included the presence or absence of ILM flap and restoration of External Limiting Membrane (ELM), Ellipsoid Zone (EZ) lines. Mean visual improvement and structural recovery were compared between eyes showing ILM flap and those showing no flap in three MH size groups. Results: Forty eyes of 38 patients with a mean age of 62.7 ± 10.1 years and a mean MH diameter of 348 ± 152 µm were included. The mean follow-up was 527 ± 478 days with anatomical closure observed in all eyes. Mean best-corrected visual acuity (BCVA) improved significantly from 0.87 ± 0.38 to 0.35 ± 0.26. ILM flap was visible in 29 (72.5%) all MHs, 7 (53.8%) small MHs (n = 13), 8 (61.5%) medium MHs (n = 13), and 14 (100%) large MHs (n = 14). The mean BCVA change was 0.47 ± 0.34, 0.53 ± 0.48, and 0.56 ± 0.20 in large, medium, and small MHs, respectively, and the difference between eyes showing ILM flap versus no flap in each MH size group was not statistically significant (P > 0.05). However, for medium MHs, it was higher in the ILM flap (0.66 ± 0.52) group compared to the no flap (0.32 ± 0.37) group. One eye with small MH developed significant gliosis resulting in reduced BCVA. ELM was restored in all eyes with small and medium MHs. Conclusion: We observed that the ILM flap did not adversely affect anatomical and visual outcomes for MHs <400 µm. Restoration of ELM suggests minimal interference in structural recovery by an ILM flap.

Lung cancer mortality in the wake of the changing smoking epidemic: a descriptive study of the global burden in 2020 and 2040.

OBJECTIVES: Lung cancer (LC) is the leading cause of cancer death in 2020, responsible for almost one in five (18.0%) deaths. This paper provides an overview of the descriptive epidemiology of LC based on national mortality estimates for 2020 from the International Agency for Research on Cancer (IARC), and in the context of recent tobacco control policies. DESIGN AND SETTING: For this descriptive study, age-standardised mortality rates per 100 000 person-years of LC for 185 countries by sex were obtained from the GLOBOCAN 2020 database and stratified by Human Development Index (HDI). LC deaths were projected to 2040 based on demographic changes alongside scenarios of annually increasing, stable or decreasing rates from the baseline year of 2020. RESULTS: LC mortality rates exhibited marked variations by geography and sex. Low HDI countries, many of them within sub-Saharan Africa, tend to have low levels of mortality and an upward trend in LC deaths is predicted for both sexes until 2040 according to demographic projections, irrespective of trends in rates. In very high HDI countries, including Europe, Northern America and Australia/New Zealand, there are broadly decreasing trends in men whereas in women, rates are still increasing or reaching a plateau. CONCLUSION: The current and future burden of LC in a country or region largely depends on the present trajectory of the smoking epidemic in its constituent populations, with distinct gender differences in smoking patterns, both in transitioning and transitioned countries. Further elevations in LC mortality are expected worldwide, raising important social and political questions, especially in low-income and middle-income countries.

Tanshinone-I for the treatment of uterine fibroids: Molecular docking, simulation, and density functional theory investigations.

Uterine fibroids (UF), most prevalent gynecological disorder, require surgery when symptomatic. It is estimated that between 25 and 35 percent of women wait until the symptoms have worsened like extended heavy menstrual bleeding and severe pelvic pain. These UF may be reduced in size through various methods such as medical or surgical intervention. Progesterone (prog) is a crucial hormone that restores the endometrium and controls uterine function. In the current study, 28 plant-based molecules are identified from previous literature and docked onto the prog receptors with 1E3K and 2OVH. Tanshinone-I has shown the best docking score against both proteins. The synthetic prog inhibitor Norethindrone Acetate is used as a standard to evaluate the docking outcomes. The best compound, tanshinone-I, was analyzed using molecular modeling and DFT. The RMSD for the 1E3K protein-ligand complex ranged from 0.10 to 0.42 Å, with an average of 0.21 Å and a standard deviation (SD) of 0.06, while the RMSD for the 2OVH protein-ligand complex ranged from 0.08 to 0.42 Å, with an average of 0.20 Å and a SD of 0.06 showing stable interaction. In principal component analysis, the observed eigen values of HPR-Tanshinone-I fluctuate between -1.11 to 1.48 and -1.07 to 1.25 for PC1 and PC2, respectively (1E3K), and the prog-tanshinone-I complex shows eigen values of -38.88 to -31.32 and -31.32 to 35.87 for PC1 and PC2, respectively (2OVH), which shows Tanshinone-I forms a stable protein-ligand complex with 1E3K in comparison to 2OVH. The Free Energy Landscape (FEL) analysis shows the Gibbs free energy in the range of 0 to 8 kJ/mol for Tanshinone-I with 1E3K and 0 to 14 kJ/mol for Tanshinone-I with the 2OVH complex. The DFT calculation reveals ΔE value of 2.8070 eV shows tanshinone-I as a stable compound. 1E3K modulates the prog pathway, it may have either an agonistic or antagonistic effect on hPRs. Tanshinone-I can cause ROS, apoptosis, autophagy (p62 accumulation), up-regulation of inositol requiring protein-1, enhancer-binding protein homologous protein, p-c-Jun N-terminal kinase (p-JNK), and suppression of MMPs. Bcl-2 expression can change LC3I to LC3II and cause apoptosis through Beclin-1 expression.

Thermal, Electrical, and Environmental Safeties of Sulfide Electrolyte-Based All-Solid-State Li-Ion Batteries.

The next generation of all-solid-state lithium-ion batteries (ASLIBs) based on solid-state sulfide electrolytes (SSEs) is closest to commercialization. Understanding the overall safety behavior of SSE-ASLIBs is necessary for their product design and commercialization. However, their safety behavior in real-life situations, such as battery exposure to high temperature, overcharge, mechanical rupture, and air exposure, remains largely unknown. Herein, we report preliminary but needed evidence of (i) significantly improved resistance to electrical shorting at high temperatures, (ii) reduced heat generation when subjected to excessive heat, (iii) tolerable harmful gas generation when subjected to air exposure followed by high-temperature heating, and (iv) high-voltage charge stability when a battery is overcharged (5.5 V charge) in SSE-based ASLIBs compared to commercial liquid electrolyte-based LIBs (LE-LIBs). Furthermore, the result shows that SSEs can self-induce a fast and effective battery shut-down capability in ASLIBs and avoid thermal runaway upon mechanical damage and exposure to air.

Preclinical study models of psoriasis: State-of-the-art techniques for testing pharmaceutical products in animal and nonanimal models.

Local and systemic treatments exist for psoriasis, but none can do more than control its symptoms because of its numerous unknown mechanisms. The lack of validated testing models or a defined psoriatic phenotypic profile hinders antipsoriatic drug development. Despite their intricacy, immune-mediated diseases have no improved and precise treatment. The treatment actions may now be predicted for psoriasis and other chronic hyperproliferative skin illnesses using animal models. Their findings confirmed that a psoriasis animal model could mimic a few disease conditions. However, their ethical approval concerns and inability to resemble human psoriasis rightly offer to look for more alternatives. Hence, in this article, we have reported various cutting-edge techniques for the preclinical testing of pharmaceutical products for the treatment of psoriasis.

Novel Biotherapeutics Targeting Biomolecular and Cellular Approaches in Diabetic Wound Healing.

Wound healing responses play a major role in chronic inflammation, which affects millions of people around the world. One of the daunting tasks of creating a wound-healing drug is finding equilibrium in the inflammatory cascade. In this study, the molecular and cellular mechanisms to regulate wound healing are explained, and recent research is addressed that demonstrates the molecular and cellular events during diabetic wound healing. Moreover, a range of factors or agents that facilitate wound healing have also been investigated as possible targets for successful treatment. It also summarises the various advances in research findings that have revealed promising molecular targets in the fields of therapy and diagnosis of cellular physiology and pathology of wound healing, such as neuropeptides, substance P, T cell immune response cDNA 7, miRNA, and treprostinil growth factors such as fibroblast growth factor, including thymosin beta 4, and immunomodulators as major therapeutic targets.