Fibroblast Cell Line Research Articles

Tailoring the Degradation Time of Polycationic PEG-Based Hydrogels toward Dynamic Cell Culture Matrices.

Poly(ethylene glycol)-based (PEG) hydrogels provide an ideal platform to obtain well-defined and tailor-made cell culture matrices to enhance in vitro cell culture conditions, although cell adhesion is often challenging when the cells are cultivated on the substrate surface. We herein demonstrate two approaches for the synthesis of polycationic PEG-based hydrogels which were modified to enhance cell-matrix interactions, to improve two-dimensional (2D) cell culture, and catalyze hydrolytic degradation. While the utilization of N,N-(bisacryloxyethyl) amine (BAA) as cross-linker for in situ gelation provides degradable scaffolds for dynamic cell culture, the incorporation of short segments of poly(N-(3-(dimethylamino)propyl)acrylamide) (PDMAPAam) provides high local cationic charge density leading to PEG-based hydrogels with high selectivity for fibroblastic cell lines. The adsorption of transforming growth factor (TGF-β) into the hydrogels induced stimulation of fibrosis and thus the formation of collagen as a natural ECM compound. With this, these dynamic hydrogels enhance in vitro cell culture by providing a well-defined, artificial, and degradable matrix that stimulates cells to produce their own natural scaffold within a defined time frame.

Exploring the Role of Inulin in Targeting the Gut Microbiota: An Innovative Strategy for Alleviating Colonic Fibrosis Induced By Irradiation.

The use of radiation therapy to treat pelvic and abdominal cancers can lead to the development of either acute or chronic radiation enteropathy. Radiation-induced chronic colonic fibrosis is a common gastrointestinal disorder resulting from the above radiation therapy. In this study, we establish the efficacy of inulin supplements in safeguarding against colonic fibrosis caused by irradiation therapy. Studies have demonstrated that inulin supplements enhance the proliferation of bacteria responsible to produce short-chain fatty acids (SCFAs) and elevate the levels of SCFAs in feces. In a mouse model of chronic radiation enteropathy, the transplantation of gut microbiota and its metabolites from feces of inulin-treated mice were found to reduce colonic fibrosis in validation experiments. Administering inulin-derived metabolites from gut microbiota led to a notable decrease in the expression of genes linked to fibrosis and collagen production in mouse embryonic fibroblast cell line NIH/3T3. In the cell line, inulin-derived metabolites also suppressed the expression of genes linked to the extracellular matrix synthesis pathway. The results indicate a novel and practical approach to safeguarding against chronic radiation-induced colonic fibrosis.

Desymmetric homologating annulation to access chiral pentafulvenes and their application in bioimaging

The architectural design of polycyclic/multisubstituted pentafulvenes has demonstrated great potential for the development of electrochromic materials and biologically active motifs. Unfortunately, the enantioselective construction of such distinctive cores with all carbon quaternary chiral centers has remained untouched to date. Herein, we disclose an enantioselective homologating annulation of cyclopent-4-ene-dione with 3-cyano-4-methylcoumarins through L-tert-leucine derived thiourea catalysis, affording a wide range of enantioenriched polycyclic multisubstituted embedded aminopentafulvenes with excellent stereocontrol (up to 99:1 er) and chemical yields up to 87%. A detailed photophysical and cytotoxicity analysis of racemic and chiral homologated adducts unveils the exceptional behavior of chiral adducts over their racemic analogs, highlighting the importance of stereoselectivity of the developed scaffolds. A cellular uptake experiment in a mammalian fibroblast cell line confirmed the potential of developed polycyclic aminopentafulvene cores as a highly promising labeling dye that can be utilized for bioimaging without any adverse effects.

STUDY OF CHEMOPREVENTIVE ROLE OF PADDY HUSK ON CERVICAL ADENOCARCINOMA HUMAN CELL LINE (HELA CELLS)

Objective: Cervical cancer is the fourth most prevalent cancer type and the fourth primary cause of cancer-related death among women worldwide. The deficiencies of current treatments, including severe side effects and the inability to prevent progression to the metastatic stage, necessitate the investigation of alternative agents. Methods: The chemopreventive approach employing natural products such as Paddy Husk is acquiring considerable traction in the scientific community. This study examined the chemopreventive effects of Paddy Husk on HeLa cervical cancer cells. Using the TBEA method, the IC50 of the husk was determined. To evaluate the antiproliferative activity with prolonged treatment exposure, HeLa cells treated with the IC50 value were incubated for 8 days. Results: The results demonstrated that Paddy Husk extract effectively inhibited the proliferation of HeLa cells throughout the duration of the treatment. Examination under the microscope revealed that Paddy Husk extract induces apoptotic characteristics, including cell contraction, membrane rounding, membrane blebbing, the formation of apoptotic bodies, and vacuolation. A mouse skin fibroblast cell line (L929) was used to assess the in vitro safety of paddy refuse extracts at various concentrations, revealing no toxic effects on normal L929 cells. Conclusion: These findings are essential for advancing our knowledge and recognizing the potential function of Paddy Husk compounds in cervical cancer chemoprevention.

Identification of anti-fibrotic and pro-apoptotic bioactive compounds from Ganoderma formosanum and their possible mechanisms in modulating TGF-β1-induced lung fibrosis

Ethnopharmacological relevanceThe Compendium of Materia Medica and the Classic of Materia Medica, the two most prominent records of traditional Chinese medicine, documented the therapeutic benefits of Ganoderma sinense particularly in addressing pulmonary-related ailments. Ganoderma formosanum, an indigenous subspecies of G. sinense from Taiwan, has demonstrated the same therapeutic properties. Aim of the studyThe aim of this study is to identify bioactive compounds and evaluate the potential of G. formosanum extracts as a novel treatment to alleviate pulmonary fibrosis (PF). Using an in-house drug screening platform, two-stage screening was performed to determine their anti-fibrotic efficacy. Methods and materialsG. formosanum was fractionated into four partitions by solvents of different polarities. To determine their antifibrotic and pro-apoptotic properties, the fractions were analyzed using two TGF-β1-induced pulmonary fibrosis cell models (NIH-3T3) and human pulmonary fibroblast cell lines, immunoblot, qRT-PCR, and annexin V assays. Subsequently, transcriptomic analysis was conducted to validate the findings and explore possible molecular pathways. The identification of potential bioactive compounds was achieved through UHPLC-MS/MS analysis, while molecular interaction study was investigated by multiple ligands docking and molecular dynamic simulations. ResultsThe ethyl acetate fraction (EAF) extracted from G. formosanum demonstrated substantial anti-fibrotic and pro-apoptotic effects on TGF-β1-induced fibrotic models. Moreover, the EAF exhibited no discernible cytotoxicity. Untargeted UHPLC-MS/MS analysis identified potential bioactive compounds in EAF, including stearic acid, palmitic acid, and pentadecanoic acid. Multiple ligands docking and molecular dynamic simulations further confirmed that those bioactive compounds possess the ability to inhibit TGF-β receptor 1. ConclusionPotential bioactive compounds in G. formosanum were successfully extracted and identified in the EAF, whose anti-fibrotic and pro-apoptotic properties could potentially modulate pulmonary fibrosis. This finding not only highlights the EAF's potential as a promising therapeutic candidate to treat pulmonary fibrosis, but it also elucidates how Ganoderma confers pulmonary health benefits as described in the ancient texts.

In vitro Wound Healing Effect of a Siddha Formulation: Gandhaga Thailam

In vitro Wound Healing Effect of a Siddha Formulation: Gandhaga Thailam

Cytotoxicity assessment and LC-MS profiling of Adansonia digitata on human gastric and osteosarcoma cancer cell lines

Adansonia digitata (Baobab) is a large, iconic tree with rich medicinal and nutritional values and its parts are used to treat various ailments. The leaves, which are edible, serve as food. In addition to its dietary use, studies on its anti-cancer properties and the specialised metabolites responsible for those properties are limited. Therefore, this study aims to characterise the anticancer properties and chemical constituents of A. digitata L. leaves. The activity of the aqueous extract was evaluated against mouse fibroblast (L929), human gastric (AGS) and osteosarcoma (MG-63) cancer cell lines using an in-vitro MTT assay. A Brine Shrimp Lethality Assay (BSLA) was performed to determine the cytotoxicity of A. digitata extract. Liquid Chromatography-Mass Spectrometry (LC-MS) analysis was employed to identify the major chemical constituents. The in-vitro MTT assay showed that the extract has anticancer potential by sensitising cell proliferation, as the IC50 values for mouse L929, AGS and MG-63 were obtained as 2923 ± 4.504, 190.9 ± 10.81 and 1834 ± 6.194 µg/mL, respectively. BSLA elicited that there was no lethality found up to 100 µg/mL. The LC-MS analysis showed the presence of catechin, vitexin, kaempherol glycoside, rutin, and other phytocompounds. Overall, this study indicated that the potential anticancer activity of the plant extract of A. digitata against AGS cell lines, in addition to its dietary use, may be significantly influenced by its specialised metabolites.

Abstract B019: Investigating Cannabis sativa bioactive compounds as an anti-cancer treatment in high-grade serous ovarian cancer

Abstract B019: Investigating <i>Cannabis sativa</i> bioactive compounds as an anti-cancer treatment in high-grade serous ovarian cancer

Pulp or Peel? Comparative Analysis of the Phytochemical Content and Selected Cosmetic-Related Properties of Annona cherimola L., Diospyros kaki Thumb., Cydonia oblonga Mill. and Fortunella margarita Swingle Pulp and Peel Extracts.

Fruit peels might be a valuable source of active ingredients for cosmetics, leading to more sustainable usage of plant by-products. The aim of the study was to evaluate the phytochemical content and selected biological properties of hydroglycolic extracts from peels and pulps of Annona cherimola, Diospyros kaki, Cydonia oblonga, and Fortunella margarita as potential cosmetic ingredients. Peel and pulp extracts were compared for their antiradical activity (using DPPH and ABTS radical scavenging assays), skin-lightening potential (tyrosinase inhibitory assay), sun protection factor (SPF), and cytotoxicity toward human fibroblast, keratinocyte, and melanoma cell lines. The total content of polyphenols and/or flavonoids was significantly higher in peel than in pulp extracts, and the composition of particular active compounds was also markedly different. The HPLC-MS fingerprinting revealed the presence of catechin, epicatechin and rutoside in the peel of D. kaki, whereas kaempferol glucoside and procyanidin A were present only in the pulp. In A. cherimola, catechin, epicatechin and rutoside were identified only in the peel of the fruit, whereas procyanidins were traced only in the pulp extracts. Quercetin and luteolinidin were found to be characteristic compounds of F. margarita peel extract. Naringenin and hesperidin were found only in the pulp of F. margarita. The most significant compositional variety between the peel and pulp extracts was observed for C. oblonga: Peel extracts contained a higher number of active components (e.g., vicenin-2, kaempferol rutinoside, or kaempferol galactoside) than pulp extract. The radical scavenging potential of peel extracts was higher than of the pulp extracts. D. kaki and F. margarita peel and pulp extracts inhibited mushroom and murine tyrosinases at comparable levels. The C. oblonga pulp extract was a more potent mushroom tyrosinase inhibitor than the peel extract. Peel extract of A. cherimola inhibited mushroom tyrosinase but activated the murine enzyme. F. margarita pulp and peel extracts showed the highest in vitro SPF. A. cherimola, D. kaki, and F. margarita extracts were not cytotoxic for fibroblasts and keratinocytes up to a concentration of 2% (v/v) and the peel extracts were cytotoxic for A375 melanoma cells. To summarize, peel extracts from all analyzed fruit showed comparable or better cosmetic-related properties than pulp extracts and might be considered multifunctional active ingredients of skin lightening, anti-aging, and protective cosmetics.

FcLR-Chitosan/Pullulan nanofibers: Boosted antibacterial activity and decreased cytotoxicity

Natural and environmentally benign electrospun polymeric nanofibers (NFs) with distinctive features, unique physiochemical and biological properties, and high susceptibility to carry non-toxic antibacterial cargoes, e.g., ferrocenyl-based compounds, have emerged as a neo-tool for killing bacteria. Here, the antibacterial FcLR-Chit/Pull NFs were fabricated through three steps: 1) synthesis of FcLR-Chit via the attachment of chitosan to Ferrocenyl Lawesson’s Reagent (FcLR), 2) blending of the FcLR-Chit at various concentrations with the natural polymer of pullulan, and 3) electrospinning. The successfully characterized FcLR-Chit/Pull NFs with a homogenous distribution of FcLR-Chit inside the pullulan matrix were thermally stable up to 270–290 ºC and mechanically stable with an increased elongation at break (EAB) (30.0–42.2%) and decreased tensile strength (TS) (1.1–2.3 MPa) compared to the pure pullulan NFs with the EAB of 19.0% and TS of 3.6 MPa. Pure pullulan NFs and FcLR-Chit/Pull NFs (0.1 wt%, 1.0 wt%, and 5.0 wt%) showed insignificant cytotoxicity on the fibroblast cell lines (L929). The antibacterial activity was detected in the trend of FcLR-Chit/Pull NFs (5.0 wt%)>FcLR-Chit powder (5.0 wt% in water)>FcLR-Chit/Pull NFs (1.0 wt%)>FcLR powder (5.0 wt% in water)>FcLR-Chit/Pull NFs (0.1 wt%)>chitosan powder (5.0 wt% in water)> pure pullulan NFs. The FcLR-Chit/Pull NFs (5.0 wt%) with an average diameter of 365 nm, insignificant cytotoxicity on L929 cells within 24 h and 48 h, and boosted antibacterial activity with the inhibition zone diameter of 1.95 mm against Gram-negative E. Coli and 1.76 mm against Gram-positive S. aureus bacteria were chosen as the optimal nanofibrous candidate for the future bactericidal applications.

Cocrystals of a coumarin derivative: an efficient approach towards anti-leishmanial cocrystals against MIL-resistant Leishmania tropica.

Leishmaniasis is a neglected parasitic tropical disease with numerous clinical manifestations. One of the causative agents of cutaneous leishmaniasis (CL) is Leishmania tropica (L. tropica) known for causing ulcerative lesions on the skin. The adverse effects of the recommended available drugs, such as amphotericin B and pentavalent antimonial, and the emergence of drug resistance in parasites, mean the search for new safe and effective anti-leishmanial agents is crucial. Miltefosine (MIL) was the first recommended oral medication, but its use is now limited because of the rapid emergence of resistance. Pharmaceutical cocrystallization is an effective method to improve the physicochemical and biological properties of active pharmaceutical ingredients (APIs). Herein, we describe the cocrystallization of coumarin-3-carboxylic acid (CU, 1a; 2-oxobenzopyrane-3-carboxylic acid, C10H6O4) with five coformers [2-amino-3-bromopyridine (1b), 2-amino-5-(trifluoromethyl)-pyridine (1c), 2-amino-6-methylpyridine (1d), p-aminobenzoic acid (1e) and amitrole (1f)] in a 1:1 stoichiometric ratio via the neat grinding method. The cocrystals 2-6 obtained were characterized via single-crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis, as well as Fourier transform infrared spectroscopy. Non-covalent interactions, such as van der Waals, hydrogen bonding, C-H...π and π...π interactions contribute significantly towards the packing of a crystal structure and alter the physicochemical and biological activity of CU. In this research, newly synthesized cocrystals were evaluated for their anti-leishmanial activity against the MIL-resistant L. tropica and cytotoxicity against the 3T3 (normal fibroblast) cell line. Among the non-cytotoxic cocrystals synthesized (2-6), CU:1b (2, IC50 = 61.83 ± 0.59 µM), CU:1c (3, 125.7 ± 1.15 µM) and CU:1d (4, 48.71 ± 0.75 µM) appeared to be potent anti-leishmanial agents and showed several-fold more anti-leishmanial potential than the tested standard drug (MIL, IC50 = 169.55 ± 0.078 µM). The results indicate that cocrystals 2-4 are promising anti-leishmanial agents which require further exploration.

Influence of oleic acid coating on the magnetic susceptibility and Fenton reaction-mediated ROS generation by the iron oxide nanoparticles

Fenton reaction-mediated reactive oxygen species (ROS) generation by the iron oxide nanoparticles (IONPs) is responsible for its antibacterial activity. In general, IONPs are surface-coated to facilitate stability, control over size, biocompatibility, solubility, etc. We hypothesize that the extent of surface coating onto the IONPs might affect Fenton reaction-mediated ROS generation, which would eventually impact its antibacterial activity. In the present study, IONPs were prepared using the co-precipitation method, and different weights of oleic acid (OA) were loaded onto the IONPs. Pristine IONPs and oleic acid-coated iron oxide nanoparticles (OA-IONPs) were characterized using Fourier transform-infrared spectroscopy, dynamic light scattering, transmission electron microscopy, X-ray diffraction, vibrating sample magnetometry, goniometer, and thermogravimetric analysis. We found that magnetic susceptibilities of the IONPs were significantly enhanced with an increase in OA loading on the IONPs. The antibacterial study showed that the percentage inhibition was inversely related to the extent of oleic acid coating on the IONPs. The dependency of ROS generation on the extent of surface coating over IONPs was demonstrated using the 2’,7’-dichlorodihydrofluorescein diacetate (DCFDA) assay. Although pristine IONPs showed the least ROS generation, they exhibited maximum percentage inhibition of bacteria. This might be due to mechanical damage to the bacterial cells because of their crystalline nature. In vitro biocompatibility study conducted on L929 fibroblast cell lines indicated that all the nanoparticle preparations were cytocompatible. This study concluded that the extent of surface coating influences the Fenton reaction-mediated ROS generation and also the magnetic susceptibilities of the IONPs.

Abrogation of methyl methanesulphonate (MMS)-induced cytotoxic and genotoxic effects of tropical fruit juice mixture on fibroblast cells

Tropical fruit juice mixture consisting of pomegranate, guava, and roselle has been proven to possess high polyphenolic composition and antioxidant capacity. The present work aimed to evaluate the cytoprotective and antigenotoxic potentials of juice mixture in methyl methanesulphonate (MMS)-induced V79 Chinese hamster lung fibroblast cell line. MTT assay showed that the IC50 value of the juice mixture was 193.33 ± 46.40 µg/mL. Cells pretreated with 6, 12, and 25 µg/mL juice mixture showed significant increment in viability (p &lt; 0.05) following induction with MMS. However, only cells co-treated with 6 and 12 µg/mL juice mixture showed protective effect (p &lt; 0.05) against MMS-induced cytotoxicity under the co-treatment setting. Comet assay showed that the tail moment and percentage of DNA in tail in cells pretreated with the juice mixture significantly decreased compared with those in positive control groups. However, under the co-treatment setting, only 12 µg/mL juice mixture showed significant reduction (p &lt; 0.05) in tail moment compared with MMS alone. In conclusion, the tropical fruit juice mixture can abrogate and protect cells from the cytotoxic and genotoxic effects of MMS, and has the potential to be developed as beneficial formulation for health preservation.

Cyclic Amines Coupled to Indole Derivatives With Improved Efflux Pump Inhibiting Activity in Bacteria and Cancer Cells.

Indole skeleton has become a significant tool in the field of anticancer and antibacterial therapeutic strategies. The modified aza-Friedel-Crafts reaction by direct coupling of different cyclic imines and indole derivatives has been explored. To investigate the scope and limitations of the reaction and observe the effect of structural modifications, our aim was to resynthesize selected compounds as well as prepare new derivatives starting from 6,7-dimethoxy-3,4-dihydroisoquinoline, (4aR,8aR)-4a,5,6,7,8,8a-hexahydroquinoxalin-2(1H)-one and 7-azaindole. Our further aim was the systematic biological evaluation of selected C-3-coupled indole and azaindole derivatives in favour of having a preliminary overview about the structure-activity relationships. The synthesis and resynthesis of selected compounds were accomplished by extension of aza-Friedel-Crafts reaction. The products have been tested on bacteria and cancer cells. The most significant efflux pump inhibiting (EPI) activity was observed in the case of 6,7-dihydrothieno[3,2-c]pyridine coupled indole derivative. The reaction of 6,7-dimethoxy-3,4-dihydroisoquinoline with 7-azaindole resulted in the most potent biofilm inhibitor product. Applying indole and 4,9-dihydro-3H-β-carboline, 6,7-dihydrothieno[3,2-c]pyridine led to the formation of a product with the highest anticancer activity. 6,7-Dimethoxy-3,4-dihydroisoquinoline skeleton and indole as an electron-rich aromatic compound have been found to be effective in the inhibition of ABCB1. The compounds presented in the study were investigated regarding different aspects of antibacterial and anticancer activities. Accordingly, some compounds were found to have antibacterial effect on Escherichia coli and Staphylococcus aureus strains, certain C-3-coupled derivatives showed toxicity on sensitive and ABCB1 efflux pump expressing colon adenocarcinoma and a normal, non-cancerous fibroblast cell lines.

Investigation of in Vitro Immunostimulating Effects of FreezeThaw Antigens against Visceral Leishmaniasis Caused by L. Infantum

Background: Visceral leishmaniasis, also known as Kala-Azar among the public, is among the notifiable infectious diseases. The fact that an effective and safe drug or vaccine formulation suitable for use on humans has not been developed causes the disease threat to continue. The aim of this study is to determine the immune system stimulating properties and cytotoxicity of the formulations obtained by combining the antigen obtained from Leishmania infantum parasites with different adjuvants. Methods: L. infantum (EP 126) antigens were obtained by the freeze-thaw method. Freund's adjuvant (Complete and Incomplete), a classical adjuvant, was used in the studies. Mouse macrophage (J774) and mouse fibroblast (L929) cell lines were used for cytotoxicity studies. Additionally, the responses at both 10ug/ml and 40ug/ml were investigated to ensure that the developed formulations were easily adaptable to in vivo. While the cytotoxicity of the formulations was determined by the MTT cell viability analysis method, the antileishmanial property was determined by the Nitric Oxide (NO) determination method. Results: It was determined that all the developed formulations did not have a toxic effect on the host cell, the immunostimulating activity increased with increasing concentration, and the highest value was obtained at a concentration of 200 µg/ml. Cell viability at the maximum concentration was found to be between 78% and 89% for both J774 and L929 cells. The highest cell viability values and NO production abilities (37% increase compared to the control group) were obtained with Incomplete Freund's adjuvant (40 ug/ml formulation). Conclusion: It has been understood that the combination of antigens obtained by the freeze-thaw method with Freunds adjuvant (incomplete) supports NO production, thus having an immunostimulating effect.

High efficacy fluconazole loaded ZnO‐poly (vinyl alcohol) nanocomposite: Interpretive breakpoints for biological applications

AbstractNanotechnology, a versatile field, holds promise in diverse applications, such as advanced pharmaceutical techniques and innovative chemical compound fabrication. Recently, the World Health Organization (WHO) has identified sepsis as a global health priority, attributing most sepsis‐related deaths to the underlying infection. Sepsis is a complex disease that manifests in various ways, depending on factors, such as pathogen involved, mode of transmission, and the patient's immune competence. This study focuses on synthesizing zinc oxide (ZnO) through an in‐situ precipitation method and employing a solution‐based technique to coat the inorganic ZnO nanomaterial with the antimicrobial drug fluconazole (FLZ), resulting in a FLZ‐ZnO composite. Further enhancement is achieved by modifying the composite with poly(vinyl alcohol) (PVA) to improve mechanical strength, physicochemical characteristics, and the interfacial network between ZnO and FLZ. Characterization through X‐ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FESEM), particle size distribution (PSD), and thermo gravimetric analysis (TGA) confirms the synthesized compounds are stoichiometric in nature. The FLZ‐ZnO‐PVA nanocomposite demonstrates significant antifungal activity against C. albicans and A. niger, as well as enhanced antibacterial activity against E. coli and S. aureus evaluated through well diffusion technique. In vitro cellular compatibility assessment using the MTT assay with NIH‐3T3 cells reveals exceptional viability (above 75%) and negligible cytotoxicity at a concentration of 1.56 μg/mL, indicating high biosafety. The FLZ‐ZnO‐PVA nanocomposite exhibits outstanding biological performance, making it a promising candidate for clinical applications in preventing sepsis and prospective infections.Highlights Developments and preparation of FLZ‐ZnO‐PVA nanocomposite. FLZ‐ZnO‐PVA nanocomposite shows optimum antimicrobial activity. FLZ‐ZnO‐PVA shows cytotoxicity against the mouse embryonic fibroblast cell line. FLZ‐ZnO‐PVA could be used as a suitable material for treatment of sepsis.

Self‐Healing, Biocompatible Injectable Hydrogel Based on Multialdehyde Moringa oleifera Gum and Carboxymethyl Chitosan: A Suitable Platform for Drug Delivery in Wound Healing Application

AbstractThis study focuses on synthesizing an injectable hydrogel (IH) using Moringa oleifera gum (MOG) with multi‐aldehyde groups (MOG‐CHO) and carboxymethyl chitosan (CMCh) through a Schiff base reaction at 37 °C. The study includes the optimal concentration of the oxidizing agent to achieve the best content of aldehydes in Moringa oleifera gum. Furthermore, the best oxidized Moringa oleifera gum decides the least gelation time. The physical properties of the optimized IH (IH‐3‐7) are assessed, including color, gel content, porosity, load‐bearing capacity, syringeability, and self‐healing capability. Structural characterization is performed using Fourier transform Infrared spectroscopy (FT‐IR) and nuclear magnetic spectroscopy (1H NMR), while scanning electron microscope (SEM) and rheometer are used to analyze surface morphology and rheological properties. IH‐3‐7 exhibits a porous structure with 35 % porosity and interconnected holes of 1.45 to 4 μm diameter. Higher swelling at pH 5.5 is shown by swelling ratio test conducted in phosphate buffer saline (PBS) at pH 7.4 and pH 5.5. Ciprofloxacin HCl (Cipro) is loaded into IH for release assays, revealing pH‐dependent drug release. In vitro, cytotoxicity assessments on L‐929 fibroblast cell lines show IH′s biocompatibility. Hydrolytic degradation of IH in PBS at pH 7.4 is also evaluated.

Isolation and Identification of Effective Probiotics on Drug-Resistant Acinetobacter baumannii Strains and Their Biofilms.

This study aimed to identify, assess, and isolate strong lactobacilli demonstrating broad antibacterial and anti-biofilm activity against drug-resistant strains of Acinetobacter baumannii. Additionally, the mechanism of inhibition of these organisms was to be determined. Over a 6-month period (from December 2021 to June 2022), 53 clinical A. baumannii strains were collected from clinical samples. Twenty probiotic strains were isolated from local dairy products. Antibacterial activity of Lactobacillus strains' cell-free supernatant (CFS) was identified using the agar well diffusion method and the microbroth dilution test. Anti-biofilm effect was performed by the microtiter plate assay. The MTT assay was also used to look into the probiotics' cytotoxic effects on the L929 fibroblast cell line. During the 6-month period, 53 clinical A. baumannii strains were obtained and identified. Out of 20 lactobacillus strains, the CFS of a lactobacillus strain (named L9) showed an inhibitory effect against all A. baumannii strains. Using the broth microdilution method, it was shown that the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of CFS extracts of L9 strains against A. baumannii strains were both ¼ mg/mL. The result of the anti-biofilm showed that the selected probiotic could inhibit biofilm formation. The most common organic acid produced by all Lactobacillus strains, according to the HPLC method, was lactic acid, which was followed by acetic acid. The L929 fibroblast cell line was used in the cytotoxicity assay, which revealed that 100% of the cells in the L929 fibroblast cell line survived treatment with successive doses of CFSs for a full day. The probiotic strain isolated from local yogurt in this study showed potential anti-biofilm and antimicrobial properties against all drug-resistant Acinetobacter isolates. Given the increasing interest in probiotic microorganisms based on their high health benefits, further studies are recommended on the mechanisms of action between probiotics and A. baumannii strains to find new solutions for biological control and treatment of these infections without the use of antibiotics.

Fabrication of porous bone scaffolds using degradable and mouldable bacterial cellulose

Bacterial cellulose (BC) is a biomaterial extensively studied in tissue engineering due to its favorable properties. Porosity, biocompatibility, biodegradability and mechanical durability are essential material properties for scaffold use in tissue engineering. This study aims to fabricate porous scaffolds using a moldable and degradable BC-HAp composite for bone tissue engineering. BC was produced by Komagataeibacter sucrofermentans under static culture conditions. The harvested BC membranes were purified and then mechanically shredded. BC oxidation was performed using different sodium periodate concentrations (0.05–0.5 M) and treatment times (0.5–12 h). Oxidized BCs (oxBC) were modified with hydroxyapatite (HAp), then were moulded, lyophilized, and characterized. The degradability of the scaffolds was determined for 45 days. Cytotoxic analysis of oxBC scaffolds was carried out for 7 days using the L929 fibroblast cell line. The oxidation degrees of the shredded BC samples were between 6.75 and 81%, which increased in line with the increasing concentration and application time of periodate. The scaffolds prepared using oxidized cellulose for 30 and 60 min (oxBC30 and oxBC60) preserved their integrity, These scaffolds showed a weight loss of 9% and 14% in 45 days, respectively. The pore distribution was between 50 and 450 µm and concentrated in the 50–150 µm range. The compression moduli were 88.72 kPa and 138.88 kPa for oxBC30-HAp and oxBC60-HAp, respectively. It was determined that oxBC did not show a significant difference in cell viability compared to the control groups and was not cytotoxic. In conclusion, degradable and more porous bone scaffolds were fabricated using mouldable oxBC.

Inhibitors of Rho/MRTF/SRF Transcription Pathway Regulate Mitochondrial Function.

RhoA-regulated gene transcription by serum response factor (SRF) and its transcriptional cofactor myocardin-related transcription factors (MRTFs) signaling pathway has emerged as a promising therapeutic target for pharmacological intervention in multiple diseases. Altered mitochondrial metabolism is one of the major hallmarks of cancer, therefore, this upregulation is a vulnerability that can be targeted with Rho/MRTF/SRF inhibitors. Recent advances identified a novel series of oxadiazole-thioether compounds that disrupt the SRF transcription, however, the direct molecular target of these compounds is unclear. Herein, we demonstrate the Rho/MRTF/SRF inhibition mechanism of CCG-203971 and CCG-232601 in normal cell lines of human lung fibroblasts and mouse myoblasts. Further studies investigated the role of these molecules in targeting mitochondrial function. We have shown that these molecules hyperacetylate histone H4K12 and H4K16 and regulate the genes involved in mitochondrial function and dynamics. These small molecule inhibitors regulate mitochondrial function as a compensatory mechanism by repressing oxidative phosphorylation and increasing glycolysis. Our data suggest that these CCG molecules are effective in inhibiting all the complexes of mitochondrial electron transport chains and further inducing oxidative stress. Therefore, our present findings highlight the therapeutic potential of CCG-203971 and CCG-232601, which may prove to be a promising approach to target aberrant bioenergetics.