Nanomedicine as potential cancer therapy via targeting dysregulated transcription factors.

Cancer as a disease possess quite complicated pathophysiological implications and is among the prominent causes of morbidity and mortality on global scales. Anti-cancer chemotherapy, surgery, and radiation therapy are some of the present-day conventional treatment options. However, these therapeutic paradigms own several retreats, including lack of specificity, non-targeted toxicological implications, inefficient drug delivery to targeted cells, and emergence of cancer resistance, ultimately causing ineffective cancer management. Owing to the advanced and better biophysical characteristic features and potentiality for the tailoring and customizations and in several fashions, nanotechnology can entirely transubstantiate the cancer identification and its managements. Additionally, nanotechnology also renders several answers to present-day mainstream limitations springing-up in anti-cancer therapeutics. Nanocarriers, owing to their outstanding physicochemical features including but not limited to their particle size, surface morphological features viz. shape etc., have been employed in nanomedicinal platforms for targeting various transcription factors leading to worthy pharmacological outcomes. This transcription targeting activates the wide array of cellular and molecular events like antioxidant enzyme-induction, apoptotic cell death, cell-cycle arrest etc. These outcomes are obtained after the activation or inactivation of several transcription factors and cellular pathways. Further, nanoformulations have been precisely calibrated and functionalized with peculiar targeting groups for improving their efficiency to deliver the drug-payload to specified and targeted cancerous cells and tissues. This review undertakes an extensive, across-the-board and all-inclusive approach consisting of various studies encompassing different types of tailored and customized nanoformulations and nanomaterials designed for targeting the transcription factors implicated in the process of carcinogenesis, tumor-maturation, growth and metastasis. Various transcription factors viz. nuclear factor kappa (NF-κB), signal transducer and activators of transcription (STAT), Cmyc and Twist-related protein 1 (TWIST1) along with several types of nanoparticles targeting these transcription factors have been summarized here. A section has also been dedicated to the different types of nanoparticles targeting the hypoxia inducing factors. Efforts have been made to summarize several other transcription factors implicated in various stages of cancer development, growth, progression and invasion, and their targeting with different kinds of nanomedicinal agents.

Advancement of cancer immunotherapy using nanoparticles-based nanomedicine.

Cancer has complex pathophysiology and is one of the primary causes of death and morbidity across the world. Chemotherapy, targeted therapy, radiation therapy, and immunotherapy are examples of traditional cancer treatments. However, these conventional treatment regimens have many drawbacks, such as lack of selectivity, non-targeted cytotoxicity, insufficient drug delivery at tumor sites, and multi-drug resistance, leading to less potent/ineffective cancer treatment. Due to its immanent biophysical property and ability to change in numerous ways, nano-technology has completely transformed how cancer is identified and treated in recent years. Furthermore, nanotechnology providing solutions to these restrictions and boosting cancer therapy. Nanoparticles are widely used nanomedicine platform in cancer immunotherapy due to their excellent physicochemical properties that include size, shape, and surface features, resulting into desirable biological interactions and have been categorized into several types. Nanoparticles can also be potentially be up taken by antigen-presenting cells that promote the cytosolic delivery of encapsulated antigens and adjuvants. Furthermore, nanoparticles can be fine-tuned and functionalized with specific moieties to promote their efficacy in targeting and delivering cargo materials to specific locations. In this review, we summarized and discussed nanoparticles and potential features to be used as carriers in cancer immunotherapy, the current status of different types of nanoparticles, and the importance of their functionalization. Furthermore, we have also discussed nanoparticles-based nanomedicine in targeted delivery of encapsulated cancer immunotherapeutic and their involvement in the modulation of the tumor microenvironment, promoting cancer immunotherapy.

Functionalized-DNA nanostructures as potential targeted drug delivery systems for cancer therapy.

Seeman's pioneer idea has led to the foundation of DNA nanostructures, resulting in a remarkable advancement in DNA nanotechnology. Over the last few decades, remarkable advances in drug delivery techniques have resulted in the self-assembly of DNA for encapsulating candidate drug molecules. The nuclear targeting capability of DNA nanostructures is lies within their high spatial addressability and tremendous potential for active targeting. However, effective programming and assembling those DNA molecules remains a challenge, making the path to DNA nanostructures for real-world applications difficult. Because of their small size, most nanostructures are self-capable of infiltrating into the tumor cellular environment. Furthermore, to enable controlled and site-specific delivery of encapsulated drug molecules, DNA nanostructures are functionalized with special moieties that allow them to bind specific targets and release cargo only at targeted sites rather than non-specific sites, resulting in the prevention/limitation of cellular toxicity. In light of this, the current review seeks to shed light on the versatility of the DNA molecule as a targeting and encapsulating moiety for active drugs in order to achieve controlled and specific drug release with spatial and temporal precision. Furthermore, this review focused on the challenges associated with the construction of DNA nanostructures as well as the most recent advances in the functionalization of DNA nanostructures using various materials for controlled and targeted delivery of medications for cancer therapy.

Caffeic Acid-Conjugated Budesonide-Loaded Nanomicelle Attenuates Inflammation in Experimental Colitis.

Ulcerative colitis is a multifactorial disease of the gastrointestinal tract which is caused due to chronic inflammation in the colon; it usually starts from the lower end of the colon and may spread to other portions of the large intestine, if left unmanaged. Budesonide (BUD) is a synthetically available second-generation corticosteroidal drug with potent local anti-inflammatory activity. The pharmacokinetic properties, such as extensive first-pass metabolism and quite limited bioavailability, reduce its therapeutic efficacy. To overcome the limitations, nanosized micelles were developed in this study by conjugating stearic acid with caffeic acid to make an amphiphilic compound. The aim of the present study was to evaluate the pharmacological potential of BUD-loaded micelles in a mouse model of dextran sulfate sodium-induced colitis. Micelles were formulated by the solvent evaporation method, and their physicochemical characterizations show their spherical shape under microscopic techniques like atomic force microscopy, transmission electron microscopy, and scanning electron microscopy. The in vitro release experiment shows sustained release behavior in physiological media. These micelles show cytocompatible behavior against hTERT-BJ cells up to 500 µg/mL dose, evidenced by more than 85% viable cells. BUD-loaded micelles successfully normalized the disease activity index and physical observation of colon length. The treatment with BUD-loaded micelles alleviates the colitis severity as analyzed in histopathology and efficiently, overcoming the disease severity via downregulation of various related cytokines (MPO, NO, and TNF-α) and inflammatory enzymes such as COX-2 and iNOS. Results of the study suggest that BUD-loaded nano-sized micelles effectively attenuate the disease conditions in colitis.

Superior Photophysical and Photosensitizing Properties of Nanoaggregates of Weakly Emissive Dyes for Use in Bioimaging and Photodynamic Therapy.

The development of luminescent dyes based on 1,1,4,4-tetracyanobuta-1,3-dienes (TCBDs) is an active research area, and a quantum yield (ΦF) of 7.8% has been achieved so far in cyclohexane by appending a fluorophore. Our novel method radically refines weakly emissive 2,3-disubstituted TCBD (phenyl-TCBD 1) (ΦF = 2.3% in CH3CN) into a water-soluble, biocompatible nanoformulation as highly emissive aggregates 1NPs ⊂ PF-127 with ΦF = 7.9% in H2O and without fluorophore conjugation. Characterization of 1NPs ⊂ PF-127 was carried out using various spectroscopic techniques, and its predominant size was found to be 80-100 nm according to transmission electron microscopy and dynamic light scattering techniques. Spectroscopic studies including Fourier transform infrared spectroscopy revealed that aggregated phenyl-TCBD particles were encapsulated in a nonluminescent triblock copolymer (PF-127)-based nanomicelles with the TCBD entrapment efficiency of 77%. With increasing water fraction, the phenyl-TCBD nanoaggregates exhibited a 3-fold higher quantum yield, a greater lifetime, and a red shift (155 nm). This remarkable enhancement in red emissivity enabled them to be used as a bioprobe for bioimaging applications and in photodynamic therapy to selectively target cancer cell lines with singlet oxygen generation capability (ΦΔ = 0.25). According to the MTT assay, compared to the native molecular form (1229 nM), the aggregated 1NPs ⊂ PF-127 (13.51 nM) exhibited dose-dependent cell death when exposed to light with 91-fold increased activity. The histoarchitectures of various vital organs (liver, kidneys, heart, lungs, and spleen) were intact when tested for in vivo biocompatibility. This study has significant implications for developing nonplanar push-pull chromophore-based dyes as biosensors and with potential applications beyond bioimaging.

Ras-Mediated Activation of NF-κB and DNA Damage Response in Carcinogenesis.

Cancer is a multi-step process during which cells acquire mutations that eventually lead to uncontrolled cell growth and division and evasion of programmed cell death. The oncogenes such as Ras and c-Myc may be responsible in all three major stages of cancer i.e., early, intermediate, and late. The NF-κB has been shown to control the expression of genes linked with tumor pathways such as chronic inflammation, tumor cell survival, anti-apoptosis, proliferation, invasion, and angiogenesis. In the last few decades, various biomarker pathways have been identified that play a critical role in carcinogenesis such as Ras, NF-κB and DNA damage.

Biomarkers of inflammation and oxidative stress in ophthalmic disorders.

The review article focuses on free radicals and oxidative stress involved in ophthalmological diseases such as retinopathy, cataract, glaucoma, etc. Oxidative stress is considered as a key factor involved in the pathology of many chronic diseases including ophthalmic complication and inflammatory process. Oxidative stress and inflammation are closely related pathophysiological processes and are simultaneously found in many pathological conditions. The free radicals produced oxidize cellular components such as lipids and phospholipids leading to lipid peroxidation and trigger the onset of retinopathy. Cataract is a significant cause of visual disability and it is proposed that the high incidence is related to oxidative stress induced by continued intraocular penetration of light and consequent photochemical generation of free radical oxidants. Glaucoma is the leading cause of irreversible blindness and comprises a group of diseases characterized by progressive optic nerve degeneration. Oxidative injury and altered antioxidant defense mechanisms in glaucoma appear to play a role in the pathophysiology of glaucomatous neurodegeneration that is characterized by death of retinal ganglion cells. The UVB radiations through this way may cause a number of diseases like photo-keratitis, pterygium, damage to epithelium, edema, and corneal cell apoptosis.Abbreviations: ROS: reactive oxygen species; RNS: reactive nitrogen species; O2.: superoxide anion; H2O2: hydrogen peroxide;. OH: hydroxyl radicals; ONOO-, ONO2-: peroxynitrite; NO: nitric oxide; IOP: intraocular pressure; RGC: retinal ganglion cells. WHO: World Health Organization; IAPB: International Agency for the Prevention of Blindness.

Thymoquinone (2-Isoprpyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects.

Cancer remains the topmost disorders of the mankind and number of cases is unceasingly growing at unprecedented rates. Although the synthetic anti-cancer compounds still hold the largest market in the modern treatment of cancer, natural agents have always been tried and tested for potential anti-cancer properties. Thymoquinone (TQ), a monoterpene and main ingredient in the essential oil of Nigella sativa L. has got very eminent rankings in the traditional systems of medicine for its anti-cancer pharmacological properties. In this review we summarized the diverse aspects of TQ including its chemistry, biosynthesis, sources and pharmacological properties with a major concern being attributed to its anti-cancer efficacies. The role of TQ in different aspects involved in the pathogenesis of cancer like inflammation, angiogenesis, apoptosis, cell cycle regulation, proliferation, invasion and migration have been described. The mechanism of action of TQ in different cancer types has been briefly accounted. Other safety and toxicological aspects and some combination therapies involving TQ have also been touched. A detailed literature search was carried out using various online search engines like google scholar and pubmed regarding the available research and review accounts on thymoquinone upto may 2019. All the articles reporting significant addition to the activities of thymoquinone were selected. Additional information was acquired from ethno botanical literature focusing on thymoquinone. The compound has been the centre of attention for a long time period and researched regularly in quite considerable numbers for its various physicochemical, medicinal, biological and pharmacological perspectives. Thymoquinone is studied for various chemical and pharmacological activities and demonstrated promising anti-cancer potential. The reviewed reports confirmed the strong anti-cancer efficacy of thymoquinone. Further in-vitro and in-vivo research is strongly warranted regarding the complete exploration of thymoquinone in ethnopharmacological context.

Nanocarrier Composed of Magnetite Core Coated with Three Polymeric Shells Mediates LCS-1 Delivery for Synthetic Lethal Therapy of BLM-Defective Colorectal Cancer Cells.

Synthetic lethality is a molecular-targeted therapy for selective killing of cancer cells. We exploited a lethal interaction between superoxide dismutase 1 inhibition and Bloom syndrome gene product (BLM) defect for the treatment of colorectal cancer (CRC) cells (HCT 116) with a customized lung cancer screen-1-loaded nanocarrier (LCS-1-NC). The drug LCS-1 has poor aqueous solubility. To overcome its limitations, a customized NC, composed of a magnetite core coated with three polymeric shells, namely, aminocellulose (AC), branched poly(amidoamine), and paraben-PEG, was developed for encapsulating LCS-1. Encapsulation efficiency and drug loading were found to be 74% and 8.2%, respectively. LCS-1-NC exhibited sustained release, with ∼85% of drug release in 24 h. Blank NC (0.5 mg/mL) exhibited cytocompatibility toward normal cells, mainly due to the AC layer. LCS-1-NC demonstrated high killing selectivity (104 times) toward BLM-deficient HCT 116 cells over BLM-proficient HCT 116 cells. Due to enhanced efficacy of the drug using NC, the sensitivity difference for BLM-deficient cells increased to 1.7 times in comparison to that with free LCS-1. LCS-1-NC induced persistent DNA damage and apoptosis, which demonstrates that LCS-1-NC effectively and preferentially killed BLM-deficient CRC cells. This is the first report on the development of a potential drug carrier to improve the therapeutic efficacy of LCS-1 for specific killing of CRC cells having BLM defects.

Precision Nanomedicine with Bio-Inspired Nanosystems: Recent Trends and Challenges in Mesenchymal Stem Cells Membrane-Coated Bioengineered Nanocarriers in Targeted Nanotherapeutics.

In the recent past, the formulation and development of nanocarriers has been elaborated into the broader fields and opened various avenues in their preclinical and clinical applications. In particular, the cellular membrane-based nanoformulations have been formulated to surpass and surmount the limitations and restrictions associated with naïve or free forms of therapeutic compounds and circumvent various physicochemical and immunological barriers including but not limited to systemic barriers, microenvironmental roadblocks, and other cellular or subcellular hinderances-which are quite heterogeneous throughout the diseases and patient cohorts. These limitations in drug delivery have been overcome through mesenchymal cells membrane-based precision therapeutics, where these interventions have led to the significant enhancements in therapeutic efficacies. However, the formulation and development of nanocarriers still focuses on optimization of drug delivery paradigms with a one-size-fits-all resolutions. As mesenchymal stem cell membrane-based nanocarriers have been engineered in highly diversified fashions, these are being optimized for delivering the drug payloads in more and better personalized modes, entering the arena of precision as well as personalized nanomedicine. In this Review, we have included some of the advanced nanocarriers which have been designed and been utilized in both the non-personalized as well as precision applicability which can be employed for the improvements in precision nanotherapeutics. In the present report, authors have focused on various other aspects of the advancements in stem cells membrane-based nanoparticle conceptions which can surmount several roadblocks and barriers in drug delivery and nanomedicine. It has been suggested that well-informed designing of these nanocarriers will lead to appreciable improvements in the therapeutic efficacy in therapeutic payload delivery applications. These approaches will also enable the tailored and customized designs of MSC-based nanocarriers for personalized therapeutic applications, and finally amending the patient outcomes.

Biomaterial-based combinatorial approach of aescin-comprised zein-coated gelatin nanoparticles alleviates synovial inflammation in experimental inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that mostly affects joints. Although RA therapy has made significant progress, difficulties including extensive medication metabolism and its quick clearance result in its inadequate bioavailability. The anti-inflammatory effect of zein was reported with other medications, but it has certain limitations. There are reports on the anti-oxidant and anti-inflammatory effect of aescin, which exhibits low bioavailability for the treatment of rheumatoid arthritis. Also, the combinatorial effect of zein with other effective drug delivery systems is still under investigation for the treatment of experimental collagen-induced rheumatoid arthritis. The focus of this study was to formulate and define the characteristics of zein-coated gelatin nanoparticles encapsulated with aescin (Ze@Aes-GNPs) and to assess and contrast the therapeutic effectiveness of Ze@Aes-GNPs towards collagen-induced RA in Wistar rats. Nanoprecipitation and the layer-by-layer coating process were used to fabricate Ze@Aes-GNPs and their hydrodynamic diameter was determined to be 182 nm. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to further validate the size, shape, and surface morphology of Ze@Aes-GNPs. When tested against foreskin fibroblasts (BJ), these nanoparticles demonstrated significantly high cytocompatibility. Both Aes and Ze@Aes-GNPs were effective in treating arthritis, as shown by the decreased edoema, erythema, and swelling of the joints, between which Ze@Aes-GNPs were more effective. Further, it was demonstrated that Aes and Ze@Aes-GNPs reduced the levels of oxidative stress (articular elastase, lipid peroxidation, catalase, superoxide dismutase and nitric oxide) and inflammatory indicators (TNF-α, IL-1ß and myeloperoxidase). The histopathology findings further demonstrated that Ze@Aes-GNPs considerably reduced the infiltration of inflammatory cells at the ankle joint cartilage compared to Aes. Additionally, immunohistochemistry examination showed that treatment with Ze@Aes-GNPs suppressed the expression of pro-inflammatory markers (COX-2 and IL-6) while increasing the expression of SOD1. In summary, the experiments indicated that Aes and Ze@Aes-GNPs lowered the severity of arthritis, and critically, Ze@Aes-GNPs showed better effectiveness in comparison to Aes. This suppression of oxidative stress and inflammation was likely driven by Aes and Ze@Aes-GNPs.

Sophorin mitigates flutamide-induced hepatotoxicity in wistar rats.

Flutamide is frequently used in the management of prostate cancer, hirsutism, and acne. It is a non-steroidal anti-androgenic drug and causes hepatotoxicity. The current study's objective is to evaluate sophorin's hepatoprotective effectiveness against flutamide-induced hepatotoxicity in Wistar rats. Sophorin is a citrus flavonoid glycoside, also known as rutin, which is a low molecular weight polyphenolic compound with natural antioxidant properties and reported to have promising hepatoprotective efficacy. In this study, sophorin was used at a dose of 100 mg/kg body weight in purified water via oral route for 4 week daily whereas, flutamide was used at a dose of 100 mg kg/b.wt for 4 weeks daily in 0.5% carboxy methyl cellulose (CMC) through the oral route for the induction of hepatotoxicity. Flutamide administration leads to enhanced reactive oxygen species (ROS) generation, an imbalance in redox homeostasis and peroxidation of lipid resulted in reduced natural antioxidant level in liver tissue. Our result demonstrated that sophorin significantly abrogate flutamide induced lipid peroxidation, protein carbonyl (PC), and also significantly increasesed in enzymatic activity/level of tissue natural antioxidant such as reduced glutathione(GSH), glutathione reductase(GR), catalase, and superoxide dismutase(SOD). Additionally, sophorin reduced the activity of cytochrome P450 3A1 in liver tissue which was elevated due to flutamide treatment. Furthermore, sophorin treatment significantly decreased the pro-inflammatory cytokines (TNF-α and IL-6) level. Immunohistochemical analysis for the expression of inflammatory proteins (iNOS and COX-2) in hepatic tissue was decreased after sophorin treatment against flutamide-induced hepatotoxicity. Moreover, sophorin suppressed the infiltration of mast cells in liver tissue which further showed anti-inflammatory potential of sophorin. Our histological investigation further demonstrated sophorin's hepatoprotective function by restoring the typical histology of the liver. Based on the aforementioned information, we are able to come to the conclusion that sophorin supplementation might benefit wistar rats with flutamide-induced hepatic damage by reducing oxidative stress and hepatocellular inflammation.

Oral delivery of aescin-loaded gelatin nanoparticles ameliorates carbon tetrachloride-induced hepatotoxicity in Wistar rats.

AIM: The liver plays a crucial role in biotransformation but it is susceptible to chemical-induced damage, known as hepatotoxicity. Traditional therapies for protecting the liver face significant challenges, including poor bioavailability, off-target effects, adverse reactions, drug breakdown, and inadequate uptake. These issues emphasize the need for precise, targeted therapeutic approaches against hepatotoxicity. MATERIALS AND METHODS: The objective of our research was to develop a customized, biocompatible, and biodegradable nanodrug delivery system for hepatoprotection. We chose collagen hydrolyzed protein, or gelatin, as the base material and utilized solvent evaporation and nanoprecipitation methods to create nanoparticles with size ranging from 130 to 155 nm. The resulting nanoparticles exhibited a spherical and smooth surface, as confirmed by scanning and transmission electron microscopy. KEY FINDINGS: Bioactive aescin (AES), into these gelatin nanoparticles (AES-loaded gel NPs), we tested these nanoparticles using a hepatotoxicity model. The results were indicating a significant reduction in the levels of key biomolecules, including NF-κB, iNOS, BAX, and COX-2 and decreased serum levels of enzymes ALT and AST. This reduction correlated with a notable alleviation in the severity of hepatotoxicity. Furthermore, the treatment with AES-loaded gel NPs resulted in the downregulation of several inflammatory and liver-specific biomarkers, including nitrite, MPO, TNF-α, and IL-6. SIGNIFICANCE: In summary, our study demonstrates that the AES-loaded gel NPs were markedly more effective in mitigating experimental hepatotoxicity when compared to the free aescin. The nanoparticles exhibited a propensity for suppressing liver damage, showcasing the potential of this targeted therapeutic approach for safeguarding the liver from harmful chemical insults.

Women and Cardiovascular Health: Unraveling Gender-Specific Factors, Risks, and Therapeutic Approaches in Contemporary Medicine.

Background and objective Cardiovascular diseases (CVDs) constitute a significant global health challenge, causing millions of deaths annually and straining healthcare systems worldwide. This study aimed to investigate and elucidate gender-specific factors, risks, and therapeutic approaches related to cardiovascular health in women within the context of contemporary medicine. Methodology We conducted a prospective observational study spanning one year (November 2022 to October 2023) at the Peshawar Medical Complex Hospital, to meticulously explore the field of women's cardiovascular health. With a diverse cohort of 435 women (age range: 18-55 years), representing various socioeconomic backgrounds and geographic locations, our study aimed to elicit comprehensive insights. Through structured interviews covering reproductive history, lifestyle, and psychosocial aspects, coupled with clinical assessments, we gathered multifaceted data. Statistical analysis was done using SPSS Statistics version 23.0 (IBM Corp., Armonk, NY). By employing descriptive and t-tests for quantitative analysis and by thematically analyzing qualitative insights, our approach ultimately sought to provide a nuanced understanding of gender-specific factors impacting women's cardiovascular health. Results The study, involving 435 women, revealed various prevalent cardiovascular risk factors. Notable findings include a high incidence of a family history of CVD (n=213, 48.96%, p=0.013), hypertension (n=207, 47.58%), hypercholesterolemia (n=114, 26.21%), elevated triglycerides (n=162, 37.24%), and diabetes (n=64, 14.71%). Physical inactivity was also significantly more common (53.56%, p=0.004) compared to those engaging in regular activity. Women-specific risk factors comprised miscarriage (n=191, 43.91%). Therapeutic preferences varied, with a majority opting for lifestyle modifications (n=263, 60.39%) and pharmacological interventions (n=331, 76.33%). Conclusions This study provides a comprehensive understanding of prevalent cardiovascular risk factors, distinctive women-specific contributors, and diverse therapeutic preferences, highlighting the importance of personalized and targeted interventions to optimize women's cardiovascular health outcomes in contemporary medicine.

A bioactive and biodegradable vitamin C stearate-based injectable hydrogel alleviates experimental inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory joint disorder affecting nearly 1% of the global population. In RA, synovial joints are infiltrated by inflammatory mediators and enzymes, leading to articular cartilage deterioration, joint damage, and bone erosion. Herein, the 9-aminoacridine-6-O-stearoyl-L-ascorbic acid hydrogel (9AA-SAA hydrogel) was formulated by the heat-cool method and further characterized for surface charge, surface morphology, rheology, and cytocompatibility. Furthermore, we evaluated the therapeutic efficacy of the 9AA-SAA hydrogel, an enzyme-responsive drug delivery system with on-and-off switching capabilities based on disease severity against collagen-induced experimental arthritis in Wistar rats. The anti-inflammatory action of the US FDA-approved drug 9-aminoacridine (9AA) was revealed which acted through nuclear receptor subfamily 4 group A member 1 (NR4A1), an anti-inflammatory orphan nuclear receptor that inhibits nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Furthermore, we have explored the role of ascorbic acid, an active moiety of 6-O-stearoyl-L-ascorbic acid (SAA), in promoting the production of collagen production through ten-eleven translocation-2 (TET2) upregulation. Targeting through NR4A1 and TET2 could be the probable mechanism for the treatment of experimental arthritis. The combination of 9AA and ascorbic acid demonstrated enhanced therapeutic efficacy in the 9AA-SAA hydrogel, significantly reducing the severity of experimental arthritis. This approach, in contrast to existing treatments with limited effectiveness, presents a promising and more effective strategy for RA treatment by mitigating inflammation in experimental arthritis.

The Intersection of Atrial Fibrillation and Coronary Artery Disease in Middle Eastern Patients. Analysis from the Jordan Atrial Fibrillation Study.

Background: There is a scarcity of clinical studies which evaluate the association of atrial fibrillation (AF) and coronary artery disease (CAD) in the Middle East. The aim of this study was to evaluate the impact of CAD on baseline clinical profiles and one-year outcomes in a Middle Eastern cohort with AF. Methods: Consecutive AF patients evaluated in 29 hospitals and cardiology clinics were enrolled in the Jordan AF Study (May 2019-December 2020). Clinical and echocardiographic features, use of medications and one-year outcomes in patients with AF/CAD were compared to AF/no CAD patients. Results: Of 2020 AF patients enrolled, 216 (10.7%) had CAD. Patients with AF/CAD were more likely to be men and had significantly higher prevalence of hypertension, diabetes, dyslipidemia, heart failure and chronic kidney disease compared to the AF/no CAD patients. They also had lower mean left ventricular ejection fraction and larger left atrial size. Mean CHA2DS2 VASc and HAS-BLED scores were higher in AF/CAD patients than those with AF/no CAD (4.3 ± 1.7 vs. 3.6 ± 1.8, p < 0.0001) and (2.0 ± 1.1 vs. 1.6 ± 1.1, p < 0.0001), respectively. Oral anticoagulant agents were used in similar rates in the two groups (83.8% vs. 82.9%, p = 0.81), but more patients with AF/CAD were prescribed additional antiplatelet agents compared to patients with AF/no CAD (73.7% vs. 41.5%, p < 0.0001). At one year, AF/CAD patients, compared to AF/no CAD patients had significantly higher hospitalization rate (39.4% vs. 29.2%, p = 0.003), more acute coronary syndrome and coronary revascularization (6.9% vs. 2.4%, p = 0.004), and higher all-cause mortality (18.5% vs. 10.9%, p = 0.002). Conclusions: In this cohort of Middle Eastern patients with AF, one in 10 patients had CAD. The coexistence of AF and CAD was associated with a worse baseline clinical profile and one-year outcomes. Clinical study registration: the study is registered on clinicaltrials.gov (unique identifier number NCT03917992).

Sinapic acid-pullulan based inflammation responsive nanomicelles for the local treatment of experimental inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints. It is one of the major causes of disability and morbidity worldwide. Administration of conventional drugs through the systemic route restricts the bioavailability of drugs, systemic toxicity, and reduced efficacy. We have introduced Rebamipide (Reb)-loaded Sinapic acid (SA)-Pullulan (PL) nanomicelles (Reb@SA-PL NMs), a nanotechnology based drug delivery system for the treatment of inflammatory arthritis. PL is a polysaccharide obtained from the fungus Aureobasidium pullulans, and SA is a bioactive polyphenol found in various plants. Both are classified by US-FDA Generally Recognised as Safe (GRAS) materials. Reb@SA-PL NMs found to be cytocompatible. Subsequently, intra-articular administration of Reb@SA-PL NMs enhances the anti-arthritic potential compared to free Reb drug in collagen-induced experimental inflammatory arthritis rat model. Reb@SA-PL NMs reduced the expression of RANKL receptor and Nf-κB. Reb@SA-PL NMs reverses the breakdown of type II collagen, MMP-13, and inhibits the pro-inflammatory markers. Reb@SA-PL NMs prevented bone erosion, cartilage degradation, joint oedema, and synovial inflammation. The results of the study demonstrated that Reb@SA-PL NMs, an enzyme-responsive drug delivery system, has excellent potential for alleviating inflammatory arthritis by blocking MMP-13 and RANKL.

Mechanism of inhibition of alpha-amylase by caffeic acid using in-vitro and in-silico techniques.

Type-two diabetes, characterised by insulin resistance or inadequate insulin production, is prevalent among adults. The α-amylase enzyme contributes to carbohydrate digestion, elevating postprandial glucose levels. Natural compounds like caffeic acid offer a solution. This study investigates α-amylase inhibition via in-vitro and in-silico methods, emphasising the connection between phenolic compounds and antidiabetic efficacy for in-silico analysis. Enzyme kinetics, IC50, and molecular docking examine caffeic acid's inhibitory action on α-amylase, comparing it with gallic acid and acarbose. Caffeic acid outperforms acarbose with an IC50 of 4.505 mg/mL versus 16.81 mg/mL, showcasing strong antidiabetic activity. Caffeic acid's superior 1,1-diphenyl-2-picrylhydrazyl (DPPH) inhibition (90.67%) compared to gallic acid (55.76%) indicates potent antioxidative and antidiabetic properties. Molecular docking reveals hydrogen bonding between caffeic acid and α-amylase. These insights lay the groundwork for phenolic-based diabetic therapies, offering less expensive treatment for diabetes patients.

Relapsing polychondritis.

This is a case report of a 67-year-old man with the rare autoimmune disease relapsing polychondritis. The patient was initially diagnosed by general practitioners with erysipelas around his left ear, which was found red, swollen, and painful. Due to the lack of effect from antibiotics, the patient was referred to an emergency department. A rheumatologist recognised the patterns of the rare disease, diagnosed the patient and initiated proper treatment. The case clarifies the difficulty in diagnosing relapsing polychondritis, mainly due to the rarity and lack of knowledge of the disease.