Gelatin-based nanoparticles and antibiotics: a new therapeutic approach for osteomyelitis?

The result of infection of bone with microorganisms is osteomyelitis and septic arthritis. Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for most of its cases (more than 50%). Since MRSA is resistant to many treatments, it is accompanied by high costs and numerous complications, necessitating more effective new treatments. Recently, development of gelatin nanoparticles have attracted the attention of scientists of biomedicine to itself, and have been utilized as a delivery vehicle for antibiotics because of their biocompatibility, biodegradability, and cost-effectiveness. Promising results have been reported with gelatin modification and combinations with chemical agents. Although these findings have been suggested that gelatin has the potential to be a suitable option for continuous release of antibiotics in osteomyelitis and septic arthritis treatment, they still have not become routine in clinical practices. The most deliver antibiotic using gelatin-derived composites is vancomycin which is showed the good efficacy. To date, a number of pre-clinical studies evaluated the utility of gelatin-based composites in the management of osteomyelitis. Gelatin-based composites were found to have satisfactory performance in the control of infection, as well as the promotion of bone defect repair in chronic osteomyelitis models. This review summarized the available evidence which provides a new insight into gelatin-derived composites with controlled release of antibiotics.

The Long Noncoding RNA PANDAR as a Prognostic and Diagnostic Biomarker in Panceratic Cancer .

Pancreatic cancer (PC) is a lethal complication in the world, affecting around half a million individuals each year. The treatment of PC is relatively difficult due to the difficulty in making an early diagnosis. Most PC patients are confronted with locally metastatic or advanced diseases in the asymptomatic phase, and about 80% have late diagnosis with metastasis. Recently, long noncoding RNAs (lncRNAs) have drawn attention as a novel biological regulation layer. They take part in the regulation of mRNA and can be used as a prognostic factor or drug target. Based on their functions as regulators of PC initiation and progress, the lncRNAs can be categorized as tumor suppressors or oncogenic. They can be considered as a target for finding new biomarkers for prognosis, diagnosis, monitoring, and treating drug response in PC. Therefore, the present study summarizes the lncRNAs role in PC and the probable strategies to deal with their expression and controlling tumorigenesis and detection of the prognosis of PC.

Nanotechnological Advances in the Diagnosis of Gynecological Cancers and Nanotheranostics.

Gynecological cancers are one of the main causes of female mortality worldwide. Despite the various strategies to reduce mortality and improve quality of life, there are still many deficiencies in the diagnosis and treatment of gynecological cancers. One of the important steps to ensure optimal cancer treatment is the early detection of cancer cells and the use of drugs to reduce toxicity. Due to the increase in systemic toxicity and resistance to traditional and conventional diagnostic methods, new strategies, including nanotechnology, are being used to improve diagnosis and reduce the severity of the disease. Nanoparticles (NPs) provide exciting opportunities to improve Gynecological Cancers (GCs) diagnosis, particularly in the initial stages. In biomedical investigations and clinical settings, NPs can be used to increase the sensitivity and specificity of recognition and/or imaging of GCs with the help of their molecular and cellular processes. To design more efficient diagnostic NPs for gynecological cancer cells or tissues, determining the specific biomarkers is of great importance. NP-based imaging agents are another solution to trace cancer cells. This review highlights the potential of some NP-based diagnostic techniques in GC detection, which could be translated to clinical settings to improve patient care.

Niosomes as a Promising Therapeutic Approach against Colorectal Cancer: A Focus on the Delivery of Chemotherapeutics and Natural Products.

Nanotechnology has emerged as an effective approach to cancer treatment, including Colorectal Cancer (CRC). While conventional treatments, such as chemotherapeutic agents, are used to manage CRC, their efficacy can be improved using drug delivery systems that enhance their bioavailability and reduce side effects. Niosomes, polymeric nanoparticles, have shown promise as biocompatible vehicles that can transport hydrophilic and lipophilic molecules. This can result in reduced drug dosage and increased efficacy. This review examines the use of niosomal formulations as a delivery platform for treating CRC and provides practical insights into their clinical applications.

The Application of Nanotechnological Therapeutic Platforms against Gynecological Cancers.

Gynecological cancers (GCs), ovarian, cervical, and endometrial/uterine cancers, are often associated with poor outcomes. Despite the development of several therapeutic modalities against GCs, the effectiveness of the current therapeutic approaches is limited due to their side effects, low therapeutic index, short halflife, and resistance to therapy. To overcome these limitations, nano delivery-based approaches have been introduced with the potential of targeted delivery, reduced toxicity, controlled release, and improved bioavailability of various cargos. This review summarizes the application of different nanoplatforms, such as lipid-based, metal- based, and polymeric nanoparticles, to improve the chemo/radio treatments of GC. In the following work, the use of nanoformulated agents to fight GCs has been mentioned in various clinical trials. Although nanosystems have their own challenges, the knowledge highlighted in this article could provide deep insight into translations of NPs approaches to overcome GCs.

Investigation of IL-6 serum level in COVID-19 patients with positive COVID-19 IgG/IgM antibody titers to check inflammation and disease progression.

OBJECTIVE: The SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19), leads to severe pathogenicity and high mortality among different communities around the world. Therefore, it is important to understand the mechanisms of virus pathogenesis and the immune system's response to prevent the further spread of this virus. This study was aimed to evaluate the relationship between the serum level of interleukin 6 and positive IgG and IgM antibody levels in patients with COVID-19 to investigate inflammation and disease progression. METHODS & MATERIALS: In this study, 10 ml of EDTA blood samples were taken from 414 COVID-19 patients. Then, the plasma was separated and the levels of IgM and IgG antibodies and interleukin 6 cytokine were evaluated by ELISA and chemiluminescence methods, respectively. All data were analyzed by SPSS 22 and GraphPad prism 9 software at the significance level of P < 0.05. RESULTS: The results of this study showed that there was no significant difference in the expression of IgM and IgG antibodies between men and women. Also, a significant increase in the mean expression of IL-6 was observed only in the high concentration range (100-〉1000 pg/ml) in men compared to women (P < 0.001). In addition, in the female population, all three concentration ranges (negative, medium, and high) of IL-6 have the highest correlation with high titers (>10 U/ml) of IgM and IgG antibodies. While, in men, all three concentration ranges of IL-6 had the highest correlation with > 10 U/ml IgM antibody titers, but in the case of IgG, the highest correlation between different concentrations of IL-6 was observed with the negative or moderate titers of this antibody and there was an inverse relationship with the high titers of IgG (>10 U/ml). CONCLUSION: As a result, the relationship between different serum levels of cytokine IL-6 with different titers of IgM and IgG antibodies was observed in both male and female populations. In general, it can be concluded that the correlation between different concentrations of IL-6 with different IgM titers was similar in both men and women, but in the case of different IgG titers, this correlation was higher in women than men.

Tolerogenic probiotics Lactobacillus delbrueckii and Lactobacillus rhamnosus promote anti-inflammatory profile of macrophages-derived monocytes of newly diagnosed patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is known as an autoimmune disorder that is characterized by the breakdown of self-tolerance, resulting in disease onset and progression. Macrophages have been implicated as a factor in the development of SLE through faulty phagocytosis of dead cells or an imbalanced M1/M2 ratio. The study aimed to investigate the immunomodulatory effects of Lactobacillus delbrueckii and Lactobacillus rhamnosus on M1 and M2 macrophages in new case lupus patients. For this purpose, blood monocytes were collected from lupus patients and healthy people and were cultured for 5 days to produce macrophages. For 48 h, the macrophages were then cocultured with either probiotics or lipopolysaccharides (LPS). Flow cytometry and real-time polymerase chain reaction were then used to analyze the expression of cluster of differentiation (CD) 14, CD80, and human leukocyte antigen - DR (HLADR) markers, as well as cytokine expression (interleukin [IL]1-ß, IL-12, tumor necrosis factor α [TNF-α], IL-10, and transforming growth factor beta [TGF-ß]). The results indicated three distinct macrophage populations, M0, M1, and M2. In both control and patient-derived macrophage-derived monocytes (MDMs), the probiotic groups showed a decrease in CD14, CD80, and HLADR expression compared to the LPS group. This decrease was particularly evident in M0 and M2 macrophages from lupus patients and M1 macrophages from healthy subjects. In addition, the probiotic groups showed increased levels of IL-10 and TGF-ß and decreased levels of IL-12, IL1-ß, and TNF-α in MDMs from both healthy and lupus subjects compared to the LPS groups. Although there was a higher expression of pro-inflammatory cytokines in lupus patients, there was a higher expression of anti-inflammatory cytokines in healthy subjects. In general, L. delbrueckii and L. rhamnosus could induce anti-inflammatory effects on MDMs from both healthy and lupus subjects.

Recent Progress in the Application of Exosome Analysis in Ovarian Cancer Management.

Exosomes are very small (nano-sized) vesicles participating in tumor development by involvement in intercellular communication mediated by transferring biocomponents. Exosomes appear to play vital roles in various cancer development, such as ovarian cancer, a common malignancy in women. Several hallmarks of ovarian cancer are reported to be affected by the exosomemediated cellular cross-talk, including modulating peritoneal dissemination and chemoresistance. Since the expression of some biomolecules, such as miRNAs and mRNA, is changed in ovarian cancer, these exo-biomolecules can be applied as prognostic, diagnostic, and therapeutic biomarkers. Also, the selective loading of specific chemotherapeutic agents into exosomes highlights these biocarries as potential delivery devices. Exosomes could be artificially provided and engineered to better target the site of interest in ovarian cancer. In the present review, we summarize the notable achievement of exosome application in ovarian cancer management to gain applicable transitional insight against this cancer.

Curcumin and Berberine Arrest Maturation and Activation of Dendritic Cells Derived from Lupus Erythematosus Patients.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease recognized by elevated activity of autoimmune cells, loss of tolerance, and decreased regulatory T cells producing inhibitory cytokines. Despite many efforts, the definitive treatment for lupus has not been fully understood. Curcumin (CUR) and berberine (BBR) have significant immunomodulatory roles and anti-inflammatory properties that have been demonstrated in various studies. This study aimed to investigate the anti-inflammatory properties of CUR and BBR on human monocyte-derived dendritic cells (DCs) with an special focus on the maturation and activation of DCs. METHODS: Human monocytes were isolated from the heparinized blood of SLE patients and healthy individuals, which were then exposed to cytokines (IL-4 and GM-CSF) for five days to produce immature DCs. Then, the obtained DCs were characterized by FITC-uptake assay and then cultured in the presence of CUR, BBR, or lipopolysaccharide (LPS) for 48 h. Finally, the maturation of DCs was analyzed by the level of maturation using flow cytometry or real-time PCR methods. RESULTS: The results showed promising anti-inflammatory effects of CUR and BBR in comparison with LPS, supported by a significant reduction of not only co-stimulatory and antigen-presenting factors such as CD80, CD86, CD83, CD1a, CD14, and HLA-DR but also inflammatory cytokines such as IL-12. CONCLUSION: CUR and BBR could arrest DC maturation and develop a tolerogenic DC phenotype that subsequently promoted the expression of inhibitory cytokines and reduced the secretion of proinflammatory markers.

Photodynamic Therapy as a Desirable Approach in the Treatment of Colorectal Cancer, with Special Focus on Photodynamic Nanotherapeutics in Immunotherapy.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide; however, there is not a convincing treatment for this disease. Limitations of conventional CRC therapies force scientists to develop novel treatment concepts for both primary care alongside adjuvant therapy. Photodynamic therapy (PDT) has been introduced as a promising therapeutic procedure for CRC mediated through theranostic principle in which special dyes, photosensitizers (PSs), are excited by near-infrared (NIR) and visible light. Recent studies showed that PDT has synergistic effects in combination with chemotherapy or immunotherapy in the treatment of CRC patients. Of note, nanoformulation of PS or immunotherapeutic agents could augment the PDT effectiveness. In this review, we summarize PDT application in CRC management with a special focus on the nanoparticles-based delivery system from the perspective of targeting deeper CRC and increased PDT efficiency, which could provide a desirable approach for clinical translation.

A glance on the role of IL-35 in systemic lupus erythematosus (SLE).

It is well known that systemic lupus erythematosus (SLE) is an auto-inflammatory disease that is characterized by chronic and widespread inflammation. The exact pathogenesis of SLE is still a matter of debate. However, it has been suggested that the binding of autoantibodies to autoantigens forms immune complexes (ICs), activators of the immune response, in SLE patients. Ultimately, all of these responses lead to an imbalance between anti-inflammatory and pro-inflammatory cytokines, resulting in cumulative inflammation. IL-35, the newest member of the IL-12 family, is an immunosuppressive and anti-inflammatory cytokine secreted mainly by regulatory cells. Structurally, IL-35 is a heterodimeric cytokine, composed of Epstein-Barr virus-induced gene 3 (EBI3) and p35. IL-35 appears to hold therapeutic and diagnostic potential in cancer and autoimmune diseases. In this review, we summarized the most recent associations between IL and 35 and SLE. Unfortunately, the comparative review of IL-35 in SLE indicates many differences and contradictions, which make it difficult to generalize the use of IL-35 in the treatment of SLE. With the available information, it is not possible to talk about targeting this cytokine for the lupus treatment. So, further studies would be needed to establish the clear and exact levels of this cytokine and its related receptors in people with lupus to provide IL-35 as a preferential therapeutic or diagnostic candidate in SLE management.

A better understanding of the role of the CTLA-CD80/86 axis in the treatment of autoimmune diseases.

Autoimmune diseases are diseases in which the regulatory mechanisms of the immune response are disturbed. As a result, the body loses self-tolerance. Since one of the main regulatory mechanisms of the immune response is the CTLA4-CD80/86 axis, this hypothesis suggests that autoimmune diseases potentially share a similar molecular basis of pathogenesis. Hence, investigating the CTLA4-CD80/86 axis may be helpful in finding an appropriate treatment strategy. Therefore, this study aims to investigate the molecular basis of the CTLA4-CD80/86 axis in the regulation of the immune response, and then its role in developing some autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. As well, the main therapeutic strategies affecting the CTLA4-CD80/86 axis have been summarized to highlight the importance of this axis in management of autoimmune diseases.

Transitional Insight into the RNA-Based Oligonucleotides in Cancer Treatment.

Conventional cancer therapies with chemodrugs suffer from various disadvantages, such as irreversible side effects on the skin, heart, liver, and nerves with even fatal consequences. RNA-based therapeutic is a novel technology which offers great potential as non-toxic, non-infectious, and well-tolerable platform. Herein, we introduce different RNA-based platforms with a special focus on siRNA, miRNA, and mRNA applications in cancer treatment in order to better understand the details of their therapeutic effects. Of note, the co-delivery of RNAs with other distinct RNA or drugs has provided safe, efficient, and novel treatment modalities for cancer treatment.

Current use of Molecular Mechanisms and Signaling Pathways in Targeted Therapy of Prostate Cancer.

Prostate cancer (PC) is identified as a heterogeneous disease. About 20 to 30% of PC patients experience cancer recurrence, characterized by an increase in the antigen termed serum prostate-specific antigen (PSA). Clinical recurrence of PC commonly occurs after five years. Metastatic castration-resistant prostate cancer (mCRPC) has an intricate genomic background. Therapies that target genomic changes in DNA repair signaling pathways have been progressively approved in the clinic. Innovative therapies like targeting signaling pathways, bone niche, immune checkpoint, and epigenetic marks have been gaining promising results for better management of PC cases with bone metastasis. This review article summarizes the recent consideration of the molecular mechanisms and signaling pathways involved in local and metastatic prostate cancer, highlighting the clinical insinuations of the novel understanding.

Natriuretic Peptides in Gastrointestinal Cancer: Biomarkers and Potential Therapeutic Targets.

Gastrointestinal (GI) cancers are an important health problem globally. Natriuretic peptides are hormones that have a crucial role in human physiology. There are a variety of treatments for GI cancer, but conventional therapies have side effects and low efficacy. Studies have demonstrated that natriuretic peptides are therapeutic in different cancer types. Natriuretic peptides are best known for their involvement in regulating blood pressure and blood volume. The anti-tumor effect exerted by natriuretic peptides is via their inhibitory effects on DNA synthesis and by their effects on apoptosis. The anti-proliferative role of natriuretic peptides has been shown in human breast cancer, prostate, colon, pancreatic, lung, ovarian, and other tumors. The roles of natriuretic peptides in these cancers are diverse and not well understood. Therefore, we have reviewed the recent literature on natriuretic peptides in GI cancers as a common malignancy in adults to assess the pathways that NPs are involved in the progression of GI cancers and its effect on the prevention or treatment of GI cancers.

Insight into RNA-based Therapies for Ovarian Cancer.

Ovarian cancer (OC) is one of the most common malignancies in women and is associated with poor outcomes. The treatment for OC is often associated with resistance to therapies and hence this has stimulated the search for alternative therapeutic approaches, including RNA-based therapeutics. However, this approach has some challenges that include RNA degradation. To solve this critical issue, some novel delivery systems have been proposed. In current years, there has been growing interest in the improvement of RNAbased therapeutics as a promising approach to target ovarian cancer and improve patient outcomes. This paper provides a practical insight into the use of RNA-based therapeutics in ovarian cancers, highlighting their potential benefits, challenges, and current research progress. RNA-based therapeutics offer a novel and targeted approach to treat ovarian cancer by exploiting the unique characteristics of RNA molecules. By targeting key oncogenes or genes responsible for drug resistance, siRNAs can effectively inhibit tumor growth and sensitize cancer cells to conventional therapies. Furthermore, messenger RNA (mRNA) vaccines have emerged as a revolutionary tool in cancer immunotherapy. MRNA vaccines can be designed to encode tumor-specific antigens, stimulating the immune system to distinguish and eliminate ovarian cancer cells. A nano-based delivery platform improves the release of loaded RNAs to the target location and reduces the off-target effects. Additionally, off-target effects and immune responses triggered by RNA molecules necessitate careful design and optimization of these therapeutics. Several preclinical and clinical researches have shown promising results in the field of RNA-based therapeutics for ovarian cancer. In a preclinical study, siRNA-mediated silencing of the poly (ADP-ribose) polymerase 1 (PARP1) gene, involved in DNA repair, sensitized ovarian cancer cells to PARP inhibitors, leading to enhanced therapeutic efficacy. In clinical trials, mRNA-based vaccines targeting tumor-associated antigens have demonstrated safety and efficacy in stimulating immune responses in ovarian cancer patients. In aggregate, RNA-based therapeutics represent a promising avenue for the therapy of ovarian cancers. The ability to specifically target oncogenes or stimulate immune responses against tumor cells holds great potential for improving patient outcomes. However, further research is needed to address challenges related to delivery, permanence, and off-target effects. Clinical trials assessing the care and effectiveness of RNAbased therapeutics in larger patient cohorts are warranted. With continued advancements in the field, RNAbased therapeutics have the potential to develop the management of ovarian cancer and provide new hope for patients.

The crosstalk between non-coding RNA polymorphisms and resistance to lung cancer therapies.

Lung cancer (LC) is one of the most common cancer-related mortality in the world. Even with intensive multimodality therapies, lung cancer has a poor prognosis and a high morbidity rate. This review focused on the role of non-coding RNA polymorphisms such as lncRNAs and miRNAs in the resistance to LC therapies, which could open promising avenue for better therapeutic response. Of note, there is currently no valid biomarker to predict lung cancer sensitivity in patients during treatment. Since genetic variations cause many challenges in treating patients, genotyping of known polymorphisms must be thoroughly explored to find desirable treatment platforms. With this knowledge, individualized treatments could become more possible in management of LC.

Regulatory NK cells in autoimmune disease.

NK cells are defined as the major components of the immunological network which exerts defense against tumors and viral infections as well as regulation of innate and adaptive immunity, shaped through interaction with other cells like T cells. According to the surface markers, NK cells can be divided into CD56dim NK and CD56bright NK subsets. CD56bright NK cells usually are known as regulatory NK cells. Once the immune system loses its self-tolerance, autoimmune diseases develop. NK cells and their subsets can be altered during autoimmune diseases, indicative of their prominent regulatory roles and even pathological and protective functions in autoimmune disorders. In this regard, activation of CD56bright NK cells can suppress activated autologous CD4+ T cells and subsequently prevent the initiation of autoimmunity. In this review article, we summarize the roles of regulatory NK cells in autoimmune disease occurrence which needs more research to uncover their exact related mechanism. It seems that targeting NK cells can be a promising therapeutic platform against autoimmune diseases.

Influence of Renin-Angiotensin System Inhibitors on the Treatment of Metastatic Renal Cancer.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are mainly known as anti-hypertensive drugs. Recent evidence suggests their anti-tumor potential against renal cancer. More than one-fourth of patients present with metastasis on their first visit. OBJECTIVE: The purpose of the current study was to examine the potential clinical impact of ACEI/ARB on metastatic renal cell carcinoma (mRCC). METHODS: We searched through several online databases, including Pubmed, Scopus, Web of Science, and Embase, to find clinical studies that have investigated the association between treatment with ACEI/ARB and the survival of patients with mRCC. The hazard ratio (HR) and 95% confidence interval (95% CI) were utilized to assess the strength of the association. RESULTS: A total of 6 studies with a total number of 2,364 patients were found eligible for the final analysis. The HR for the relationship between ACEI/ARB use and overall survival (OS) showed patients undergoing treatment with ACEI/ARB to have higher OS than non-users (HR: 0.664, 95% CI 0.577-0.764, p=0.000). Furthermore, the HR for the relationship between ACEI/ARB use and progression-free survival (PFS) showed patients undergoing treatment with ACEI/ARB to have higher PFS than non-users (HR: 0.734, 95% CI 0.695-0.794, p=0.000). CONCLUSION: The results of this review offer ACEI/ARB as a potential therapeutic option associated with improved survival outcomes in patients receiving anti-vascular endothelial growth factor therapy.

Impacts of Porphyromonas gingivalis periodontitis on rheumatoid arthritis autoimmunity.

In RA patients' synovial sites, citrullinated RA-related antigens such as type II collagens, fibrin (ogen), vimentin, and α-enolase could be targeted by ACCPAs. Since ACCPA production can be initiated a long time before RA sign appearance, primary auto-immunization against these citrullinated proteins can be originated from extra-articular sites. It has been shown that there is a significant association between P. gingivalis periodontitis, anti- P. gingivalis antibodies, and RA. P. gingivalis gingipains (Rgp, Kgp) can degrade proteins such as fibrin and α-enolase into some peptides in the form of Arg in the C-terminal which is converted to citrulline by PPAD. Also, PPAD can citrullinate type II collagen and vimentins (SA antigen). P. gingivalis induces inflammation and chemoattraction of immune cells such as neutrophils and macrophages through the increase of C5a (gingipain C5 convertase-like activity) and SCFA secretion. Besides, this microorganism stimulates anoikis, a special type of apoptosis, and NETosis, an antimicrobial form of neutrophil death, leading to the release of PAD1-4, α-enolase, and vimentin from apoptotic cells into the periodontal site. In addition, gingipains can degrade macrophages CD14 and decrease their ability in apoptotic cell removal. Gingipains also can cleave IgGs in the Fc region and transform them into rheumatoid factor (RF) antigens. In the present study, the effects of P. gingivalis on rheumatoid arthritis autoimmune response have been reviewed, which could attract practical insight both in bench and clinic.