Introduction. Endometriosis is a chronic hormone-dependent inflammatory disease determined by the presence of foci of endometrial tissue outside the uterine cavity. Genetic factors occupy a leading position in the etiopathogenesis of this disease. The aim of the study: To study the associations of polymorphism of sex hormone genes with the hormonal profile of patients with endometriosis. Materials and methods: the study group included 103 patients with endometriosis, who were examined for levels of sex hormones (follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, progesterone, testosterone and dehydroepiandrosterone). The genotyping of 9 single nucleotide polymorphisms (SNP) of GWAS-significant sex hormone genes was carried out. The associations of SNPs with the level of sex hormones in patients with endometriosis were investigated by linear regression. Results: among patients with endometriosis, the serum estradiol level is associated with polymorphic loci rs148982377 ZNF789 (β=-0.488 - -0.445, p_perm≤0.050) and rs34670419 ZKSCAN5 (β=-0.544 - -0.449, p_perm≤0.050), luteinizing hormone – rs117585797 ANO2 (β= 0.618 - 0.709, p_perm≤0.050), progesterone – rs117145500 CHD9 (β=0.365 - 0.429, p_perm<0.050), prolactin – rs1641549 TP53 (β=-0.306 - -0.218, p_perm<0.050), testosterone – rs148982377 ZNF789 and rs34670419 ZKSCAN5 (β=0.492, p_perm=0.050). Conclusion: Associations of candidate gene polymorphism with the level of sex hormones in patients with endometriosis have been established.

Inflammatory Bowel Disease, is a term used for chronic inflammatory condition that includes two diseases i.e., Ulcerative Colitis and Crohn’s Disease, both mostly affect the colon, as well as the mouth, oesophagus, stomach, small intestine, and large intestine, respectively. If untreated, it may cause the gut to become more constricted, rupture, produce holes, fistulas, and—most alarmingly colon cancer. One of the key signalling pathways reported to be important in IBD and Colon Cancer is the Keap1/Nrf2. According to several studies, Keap1/Nrf2 is also implicated in T-cell differentiation and inflammation; it can block IL-17, Th1 and Th17 generation and stop the production of various other pro-inflammatory cytokines. Most fruits and vegetables contain polyphenols, which are recognized by possessing more than one phenolic group. By destroying Keap1, these polyphenols can activate a pathway connected to Nrf2, continuous improvement in polyphenol extraction and purification, as well as research on the molecular mechanism of Keap1/Nrf2 in numerous polyphenol monomers that can control Nrf2 have been found during the past decade. Therefore, a molecular docking research was carried out to assess how Keap1/Nrf2 interacted with the common polyphenols found in Krishna Tulsi (Ocimum Tenuiflorum L.) such as Syringic acid, Caffeic acid, Ferulic acid, Catechin and Epicatechin. Catechin was found to have least binding energy of -9.3 kcal/mol that indicates the high binding affinity between the chosen receptor and ligand. The contact residue includes GLY364; LEU365; ALA366; GLY367; CYS368; ILE416; GLY417; VAL418; GLY462; VAL463; GLY464; VAL465; GLY509; ALA510; GLY511; VAL512; CYS513; LEU557; GLY558; ILE559; THR560; VAL561; GLY603; VAL604; GLY605; VAL606 and ALA607. To verify these results in IBD, however, more in-vitro, and in-vivo research is necessary.

The ever increasing bacterial resistance towards antibiotics has become a global concern that conditions and put the lives of many patients at risk. Natural extracts are emerging as potential alternatives to the use of antibiotics to fight infections, by exhibiting excellent antimicrobial and anti-inflammatory profiles. The biomolecules thymol, eugenol, carvacrol and propolis have been explored in the prevention/treatment of wound infections, revealing great effectiveness. Different fiber-based scaffolds have been employed in wound therapies because of their similarities to the fibrillar elements that make up the structure of the skin. In this study, we explored the antimicrobial profiles of selected natural extracts and their potential for incorporation into wet-spun fibers. In a first instance, the antibacterial potential of the former four extracts was examined against the Gram-positive bacteria Staphylococcus aureus and Staphylococcus epidermidis. Thymol was highlighted as the most effective from the group, registering minimal inhibitory concentrations (MIC) of 0.313 and 0.627 mg/mL against each bacterium, respectively. Propolis displayed MICs of 2.560 mg/mL, while carvacrol registered MICs of 2.560 and 5.120 mg/mL against S. aureus and S. epidermidis, respectively. On its turn, eugenol required the highest concentrations, 5.120 mg/mL, to induce the same effect as the other extracts. Thymol exhibits different mechanisms of action against bacteria: it can destroy the integrity of the cell membrane and/or destabilize the secondary structure of bacterial DNA, compromising the viability of the microorganism, which can explain its superior effectiveness compared to the remainder extracts. Subsequently, polycaprolactone (PCL) wet-spun fibers were produced and functionalized with thymol. Using the wet-spinning technique, 9 wt.% PCL in dimethylformamide was processed in the form of fibers at an extrusion rate of 0.1 mL/min directly into a distilled water (dH₂O) coagulation bath. To generate modified fibers, the PCL solution was combined with thymol (dissolved in dimethyl sulfoxide) at 1.254 mg/mL (2×0.627 mg/mL; 2×MBC). Both PCL and PCL-thymol fibers presented a uniform and homogeneous appearance. Presence of thymol reduced the elongation at break (from 159.32 to 93.26%) and diameter of the fibers (from 247.49 to 146.99 µm). In a near future, individual PCL fibers loaded with thymol will be combined and knitted in the form of a dressing system with an effective antibacterial profile for potential uses in wound infection control.

Enteroaggregative Escherichia coli (EAEC) is an emerging bacterial pathogen implicated in gastrointestinal illnesses world-wide and has been documented as one of the foremost causes of acute and persistent diarrhea in children and adults. Of late, an unusual emergence of multi-drug resistance among EAEC strains has been recognized globally; hence the emphasis has been given to adjuvant therapies to combat this nagging public health threat. Nanotechnology has recently received much interest in the wake of antimicrobial resistance (AMR) and is seen to be a promising interventional tool for treating drug-resistant infections. This study assessed the antibacterial efficacy of green synthesized ZnO NPs using aqueous extract of Piper longum catkin against multi-drug resistant strains of enteroaggregative Escherichia coli (MDR-EAEC). Initially, the synthesis of ZnO NPs was confirmed by UV- Vis spectroscopy and Fourier transform infra- red spectroscopy (FTIR) analysis. The TGA/DTA revealed thermal stability of ZnO NPs, while a hexagonal wurtzite crystalline structure was exhibited by PXRD analysis, which was further confirmed by SEM and TEM. The minimum inhibitory concentration as well as minimum bactericidal concentration of bio-fabricated ZnO NPs determined by microbroth dilution technique against MDR-EAEC (n= 3) strains revealed 125 μg/mL and 250 μg/mL, respectively. In addition, ZnO NPs were tested variably stable (high-end temperatures, physiological concentration of salts, proteases and varying pH) and safe (chicken RBCs, HEK cell lines, gut lactobacilli). The green synthesized ZnO NPs exhibited a concentration- dependent antioxidant activity as evidenced by ABTS assay and reducing power assay. Furthermore, the green synthesized ZnO NPs inhibited the biofilm forming ability of the tested MDR-EAEC strains. Overall, this study demonstrated an eco- friendly one-pot synthesis of ZnO NPs, which could be employed as a potential antimicrobial alternative candidate against MDR-EAEC strains.

Acute localized irradiation accidents may evolve into a cutaneous radiation-induced syndrome (CRS) which leaves a significant underlying muscle defect despite a standard treatment. It is therefore necessary to identify new therapeutic targets to improve post-irradiation muscle regeneration.

Thus, the validation of an in vivo model of spontaneously regenerating radiation-induced muscle lesions has been initiated. The left gastrocnemius/soleus muscles of C57Bl/6 mice were irradiated with a 60 Gy X-ray dose, with a beam collimation of 9x3mm. A weekly follow-up of muscle strength and lesions was carried. Then macroscopic, biochemical and histological muscular radiation-induced effects were analyzed at day 90 post-irradiation.

The functional test revealed a contraction of the irradiated left paw compared to the right paw of the same mice. Scoring of skin lesions located on the left paw showed an increase in skin damage over time. Interestingly, studies performed at day 90 on tissue samples showed muscle atrophy after radiation exposure with a decrease of muscle weight and fibers diameter, suggesting a degeneration concomitant or not with regeneration. Finally, variations in specific muscle (Pax7, Myf5, MyoG, Myosin isoforms) and inflammatory (IL-1 beta, TGF beta, IL-10) markers have been highlighted between irradiated and control groups by gene expression analysis.

Following this preliminary study, a more complete kinetic study is underway, performed at early, intermediate and late time points, in order to analyze the spontaneous muscle regeneration capacity of the muscle after a highly localized irradiation at different doses. Thus, a major scientific interest lies in this project to improve the understanding of muscle degeneration and regeneration in CRS, allowing the identification of new therapeutic targets and the development of innovative medical countermeasures.

Santolina chamaecyparissus, also known as cotton-lavender, is a small, compact ever green plant with greyish leaves and yellow inflorescences that bloom in the summer. It is part of the Asteraceae family. This plant can be found locally on both the European and American Continents as well as the western and central Mediterranean regions. It is regarded as an aromatic plant and has been used in folk medicine for a variety of medical conditions, including the relief of premenstrual syndrome, the treatment of infection diseases and digestive disorders. A better understanding of this plant's chemical composition has revealed novel properties that can be used in modern medicine. This plant's extracts have been shown to provide a variety of therapeutic effects, including antineoplastic, anti-inflammatory, antioxidant, antimicrobial, antifungal, CNS depressant, and anti-cholinergic. In order to further our understanding of the potential health effects of this species, it is therefore worthwhile to invest in clinical research of this plant's extracts. This work reviews the current research on Santolina chamaecyparissus that shows its potential application as a novel treatment approach in modern medicine, making it a functional food and nutraceutical.

Blue LED light (410-430 nm) induces hemostasis through a photo-thermo-coagulation process, mediated by the absorption of the light from macromolecules naturally present in tissues, such as hemoglobin or even the cytochrome C. These macromolecules can trigger intracellular pathways, which are involved in the healing process. Clinical evidence of PhotoBioModulation (PBM) has been observed, and blue-light treatment is successfully used in dermatological practice and in wound management. Here, we describe the effects of the one-time application of 20.6 J/cm² of blue LED light in two murine models: superficial and full-thickness wounds. In the first model (33 CD1 mice), the inflammatory response was studied: neutrophils, mast cells and their degranulation index, M1 and M2 macrophages, and endothelial cells were investigated after 1-3-6-9-12-18-24-72-144 hours from the wound induction by histology and immunofluorescence analysis. In the second model, 63 CD1 mice were randomized into three groups: in two groups one wound was performed, while two wounds were induced in the other group. Only one wound was treated by applying 20.6 J/cm² of blue light. The animals were sacrificed after 1-3-6-9- 24 hours and 7-14 days after the treatment. An ELISA assay was used to study EGF, bFGF, VEGF, TNF-α, MMP-2 and pro-MMP-9. Our findings show that the treated samples have a higher immunity reaction in the time span between 1 and 9 hours, but a lower degree of inflammation after 24 hours. After 24 hours, an increase in mast-cell density and their degranulation index correlated to the expression of the MHC was found. The expression of bFGF, EGF and Pro-MMP-9 evidenced a modulation due to the light treatment. These results demonstrated that blue-LED-light PBM stimulates an earlier activation of the first phases of wound healing, leading to a faster recovery of the wounded tissue. On these bases, blue LED light can be considered a valid additional treatment to standard therapies in wound management.

Chronic wounds (CW) are a worldwide concern, causing serious strives on the health and quality of patients’ life. In CW, human neutrophil elastase (HNE) enzyme gets highly expressed during inflammation, reaching abnormally elevated concentrations. Additionally, prevalence of Staphylococcus aureus-induced infections remains very high and difficult to treat. Considering these phenomena, a drug delivery system made of coaxial wet-spun fibers, loaded with the tetrapeptide Ala-Ala-Pro-Val (AAPV, a known inhibitor of HNE activity) and N-carboxymethyl chitosan (NCMC, responsive to neutral-basic pH’s, characteristic of CW and endowed with antibacterial features), was proposed.

AAPV was synthesized by solid-phase peptide synthesis, whereas NCMC was synthesized from low molecular weight chitosan in a chloroacetic acid mixture. HNE inhibition tests were conducted to establish the AAPV IC₅₀ in 50 µg/mL and the NCMC minimum bactericidal concentration (MBC) against S. aureus in 3.072 mg/mL. These determinations were used to establish fiber loading amounts. Core-shell structures were produced with 10% w/v polycaprolactone (PCL) at the core and 2% w/v sodium alginate (SA) solutions at the shell. NCMC was mixed with SA at 2xMBC so neutral-basic pH-triggered solubility (characteristic of CW) would allow pores to be opened in the outer layer for accessing the core, where AAPV was combined with PCL.

Fourier-transform infrared spectroscopy and brightfield microscopy were used to confirm the presence of the four components on the fibers and the co-axial architecture, respectively. Fibers presented maximum elongations of over 100%. A chemically modified version of AAPV was synthesized by including a fluorescent group (Fmoc), attached to the last amino acid of AAPV, due to an overlapping of maximum absorbances between all fiber compounds, making it impossible to analyze AAPV release profile. Release kinetics studies were then conducted via spectrofluorimetry, which successfully mapped AAPV liberation overtime. Time-kill kinetics studies against S. aureus demonstrated the effectiveness of NCMC in eliminating this bacterium, particularly after 6 h of incubation. On its turn, AAPV guaranteed HNE inhibition. Data demonstrated the potential of SA-NCMC-PCL-AAPV coaxial systems to work as stepwise, pH-triggered delivery platforms.

Circulating tumor cells (CTCs) are detected before the appearance of other signs of lung cancer, including precancerous conditions. CTCs and cancer stem cells (CSCs) play a leading role in metastasis of small cell lung cancer (SCLC) and can be used as diagnostic and prognostic markers, potential therapeutic targets. Cell therapy with modified immune cells is a promising approach for the treatment of SCLC. An unresolved issue of this approach to therapy is the choice of the optimal cell donor whose modified cells could eliminate the given target of CSCs. In the present study, using in vitro allogeneic and autologous cell therapy model, we reprogrammed CD8⁺ T-cells isolated from the blood of healthy volunteers (non-smoker and smoker) and patients with chronic lung diseases (chronic obstructive pulmonary diseases (COPD), SCLC and asthma in different combination) and assessed their survival and cytotoxic activity relative to CSCs of a patient with SCLC and COPD. Reprogramming with MEK and PD-1 inhibitors, and targeted “training” with CSCs isolated from the blood of the patient with SCLC and COPD increased the survival and cytotoxic activity of allogeneic CD8⁺ T-cells from all subjects in vitro. At the same time, the positive effect of reprogramming is more pronounced in patients with lung diseases that in healthy donors. Autologous reprogrammed CD8⁺ T-cells was shown to be highly effective in eliminating CSCs in a patient with SCLC and COPD. Thus, in vitro studies are significant in selection of a potential cell donor and evaluating the effectiveness of their reprogramming.

Insulin is a peptide hormone that has a number of physiological functions, and in particular, is involved in the regulation of blood glucose levels. The hormone has been found to affect wound healing by reducing inflammation, regulating oxidative reactions, and increasing collagen deposition. Despite the many benefits of insulin, there is still no topical preparation on the skin on the market. The problem is the lack of stability of this peptide in the wound bed. The presence of proteases in the wound environment deactivates the hormone. Research efforts undertaken in recent years to develop a topical form of insulin have focused on designing an effective carrier to improve the stability of the peptide drug. The aim of this study was to review the literature on the development of a hydrogel formulation of insulin to promote wound healing and to identify the benefits of this carrier. An analysis of papers published between 2000 and 2022 was carried out. Embase, Medline, PubMed, and Cochrane Library databases were used. Keywords used: hydrogel, polymers, insulin, topical, diabetic ulcers, wound healing, chronic wounds. Conference abstracts and non-English language articles were omitted. 12 publications met the search criteria. The literature analysis confirmed that topical insulin administration improves wound healing without significantly affecting the occurrence of side effects. Hydrogels may provide a starting point for developing new or improving the efficacy of designed epidermal forms of insulin. The hydrogels used (poly(vinyl alcohol), chitosan, alginate, Aloe vera, Pluronic F127 carbomer, and keratin) allow efficient delivery of the peptide into the wound environment. We believe that work on insulin preparations should continue, allowing the mechanism of action of this hormone on wounds to be explored and an effective preparation to be developed for clinical use. Hydrogels are a promising direction for insulin carrier development.