Gentamicin Research Articles

Assessment of performance and safety of Corneal Chamber hypothermic storage medium and PSS-L corneal rinsing solution in human and porcine corneas

PurposeTo prove the safety and performance of the hypothermic corneal storage medium "Corneal Chamber" and the rinsing solution "PSS-L" in support of the new Conformité Européenne (CE) certification process in...

Monoterpene linalool restrains gentamicin-mediated acute kidney injury in rats by subsiding oxidative stress, apoptosis, and the NF-κB/iNOS/TNF-α/IL-1β pathway and regulating TGF-β.

The clinical use of gentamicin (GM) is restricted by its nephrotoxic effects. This study aimed for the first time to elucidate the ameliorative effects of the monoterpene linalool (Lin) against GM-mediated acute kidney injury in rats. A total of thirty-two rats were subdivided into four equal groups: control (saline), Lin (100mg/kg/day), GM (100mg/kg/day), and GM + Lin (100 and 100mg/kg/day). Lin and GM were intraperitoneally administered for 12 days. Our results illustrated that Lin ameliorated GM-mediated renal histopathological abnormalities and reduced serum urea and creatinine levels in rats exposed to GM. Lin treatment mitigated oxidative stress in nephrotoxic animals as manifested by reducing serum and renal levels of malondialdehyde and increasing the activities of serum and renal glutathione peroxidase and renal catalase. Moreover, Lin markedly inhibited GM-triggered inflammation by downregulating NF-κB, iNOS, TNF-α, and IL-1β and reducing renal myeloperoxidase activity and nitric oxide levels. Interestingly, Lin repressed GM-induced apoptosis, as reflected by a marked downregulation of Bax and caspase-3 expression, concurrent with the upregulation of Bcl2 expression. Finally, Lin administration led to a significant downregulation of TGF-β expression in nephrotoxic animals. In summary, Lin ameliorated GM-mediated nephrotoxicity in rats, at least through its antioxidant, anti-inflammatory, and anti-apoptotic activities and by modulating TGF-β.

Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms

BackgroundWhile antibiotics remain our primary tools against microbial infection, increasing antibiotic resistance (inherent and acquired) is a major detriment to their efficacy. A practical approach to maintaining or reversing the efficacy of antibiotics is the use of other commonly used therapeutics, which show synergistic antibacterial action with antibiotics. Here, we investigated the extent of antibacterial synergy between the antibiotic gentamicin and the anti-inflammatory ketorolac regarding the dynamics of biofilm growth, the rate of acquired resistance, and the possible mechanism of synergy.MethodsControl (ATCC 12600, ATCC 35984) and clinical strains (L1101, L1116) of Staphylococcus aureus and Staphylococcus epidermidis with varying antibiotic susceptibility profiles were used in this study to simulate implant-material associated low-risk and high-risk biofilms in vitro. The synergistic action of gentamicin sulfate (GS) and ketorolac tromethamine (KT), against planktonic staphylococcal strains were determined using the fractional inhibitory concentration measurement assay. Nascent (6 h) and established (24 h) biofilms were grown on 316L stainless steel plates and the synergistic biofilm eradication activity was determined and characterized using adherent bacteria count, minimum biofilm eradication concentration (MBEC) measurement for GS, visualization by live/dead imaging, scanning electron microscopy, gene expression of biofilm-associated genes, and bacterial membrane fluidity assessment.ResultsGentamicin-ketorolac (GS-KT) combination demonstrated synergistic antibacterial action against planktonic Staphylococci. Control and clinical strains showed distinct biofilm growth dynamics and an increase in biofilm maturity was shown to confer further resistance to gentamicin for both ‘low-risk’ and ‘high-risk’ biofilms. The addition of ketorolac enhanced the antibiofilm activity of gentamicin against acquired resistance in staphylococcal biofilms. Mechanistic studies revealed that the synergistic action of gentamicin–ketorolac interferes with biofilm morphology and subverts bacterial stress response altering bacterial physiology, membrane dynamics, and biofilm properties.ConclusionThe results of this study have a significant impact on the local administration of antibiotics and other therapeutic agents commonly used in the prevention and treatment of orthopaedic infections. Further, these results warrant the study of synergy for the concurrent or sequential administration of non-antibiotic drugs for antimicrobial effect.

Reduced graphene oxide-gadolinium oxide-functionalized paper based immunosensor for electrochemical detection of gentamicin

Excessive consumption of antibiotics like gentamicin (GEN) can lead to hostile effects as antibiotic resistance. Therefore, the detection is important for which, reduced graphene oxide-Gadolinium oxide nanocomposite (rGO@Gd2O3 NC) was composed through co-precipitation method for the detection of GEN. The structural, morphological and functional group characterizations were done using XRD, FT-IR, SEM and TEM techniques. The cyclic voltammetry (CV) showed excellent electrocatalytic activity and superior performance towards GEN detection. Through the use of GEN monoclonal antibodies (anti-GEN) on a screen-printed electrode (SPE), a very sensitive electrochemical immunosensor was fabricated. Covalent interactions were employed to construct the electrochemical immunosensor, while bovine serum albumin (BSA) was employed as a blocking agent on the anti-GEN/rGO@Gd2O3/SPE electrode surface. The analysis of the CV response of the BSA/anti-GEN/rGO@Gd2O3/SPE bioelectrode demonstrated linear detection range from 1 pM – 100 μM, along with limit of detection (LOD) of 0.424 pM and sensitivity of 44.87 μA pM-1 cm− 2. Additionally, rGO@Gd2O3 immunosensor, exhibited a good level of linearity with R2 value of 0.978. These findings indicate the excellent potential of the rGO@Gd2O3 electrochemical immunosensor for accurately detecting GEN in spiked milk samples at different concentrations.

Exploring PLGA-OH-CATH30 Microspheres for Oral Therapy of Escherichia coli-Induced Enteritis.

Antibiotic therapy effectively addresses Escherichia coli-induced enteric diseases, but its excessive utilization results in microbial imbalance and heightened resistance. This study evaluates the therapeutic efficacy of orally administered poly (lactic-co-glycolic acid) (PLGA)-loaded antimicrobial peptide OH-CATH30 microspheres in murine bacterial enteritis. Mice were categorized into the healthy control group (CG), untreated model group (MG), OH-CATH30 treatment group (OC), PLGA-OH-CATH30 treatment group (POC), and gentamicin sulfate treatment group (GS). Except for the control group, all other experimental groups underwent Escherichia coli-induced enteritis, followed by a 5-day treatment period. The evaluation encompassed clinical symptoms, intestinal morphology, blood parameters, inflammatory response, and gut microbiota. PLGA-OH-CATH30 microspheres significantly alleviated weight loss and intestinal damage while also reducing the infection-induced increase in spleen index. Furthermore, these microspheres normalized white blood cell count and neutrophil ratio, suppressed inflammatory factors (IL-1β, IL-6, and TNF-α), and elevated the anti-inflammatory factor IL-10. Analysis of 16S rRNA sequencing results demonstrated that microsphere treatment increased the abundance of beneficial bacteria, including Phocaeicola vulgatus, in the intestinal tract while concurrently decreasing the abundance of pathogenic bacteria, such as Escherichia. In conclusion, PLGA-OH-CATH30 microspheres have the potential to ameliorate intestinal damage and modulate the intestinal microbiota, making them a promising alternative to antibiotics for treating enteric diseases induced by Escherichia coli.

Dynamic responses of Salmonella Typhimurium to re-exposure to sublethal ciprofloxacin.

This study was designed to evaluate the history-dependent behaviors of Salmonella Typhimurium re-exposed to sublethal levels of ciprofloxacin. The S. Typhimurium cells were pre-exposed to 0 (CON), 1/16 (LOW), 1/8 (MED), and 1/4 (HIGH) minimum inhibitory concentrations (MICs) of ciprofloxacin, followed by re-exposure to the same concentrations. The bacterial growth, postantibiotic effect (PAE), relative fitness, and swimming motility of treatments were evaluated in the absence of ciprofloxacin. The lag phase duration (LPD) was estimate to assess bacterial recovery under ciprofloxacin exposure. A disk diffusion assay was used to determine the cross-resistance and collateral sensitivity of CON, LOW, MED, and HIGH treatments to ciprofloxacin (CIP), ceftriaxone (CEF), erythromycin (ERY), gentamicin (GEN), and polymyxin B (POL). The S. Typhimurium cells pre-exposed to ciprofloxacin were susceptible in antibiotic-free media, showing delayed growth. The highest PAE (>1h) and bacterial fluctuation (CV=5%) were observed at the High treatment compared to the CON. The HIGH treatment had the lowest relative fitness levels (0.87) and swimming motility (55mm). The LPD was significantly decreased at the LOW treatment (1.8h) when re-exposed to 1/16×MIC of ciprofloxacin. The LOW, MED, and HIGH treatments showed the cross-resistance to POL and the collateral sensitivity to CEF, ERY, and GEN. The pre-exposure to ciprofloxacin could induce phenotypic diversity, corresponding to the history-dependent behaviors. These results provide important insights for the dynamic nature of bacterial populations when re-exposed to sublethal concentrations of antibiotics.

Effect of cumulus cells and duration of culture on nuclear maturation of oocytes of pubertal and pre-pubertal individuals from Sus scrofa domesticus

Objective: to evaluate the nuclear maturation ability of pig oocytes in relation to the morphology of the surrounding cumulus cells, the duration of in vitro maturation (IVM) and the physiological status of cumulus-oocyte complexes (COCs) donor animals.Materials and methods. СOCs collected from cycling (pubertal) and non-cycling (prepubertal) pigs ovaries were categorized according to the number of cumulus cell (CC) layers: COC I – more then 4, COC II – 3-4, COC III – 1-2 and СOC with granulosa cells (GCOC). Oocytes within COCs were matured during the first 22 h of culture in the TC-199 medium with 25 mM HEPES, 3.05 mM D-glucose, 0.91 mM sodium pyruvate, 0.57 mM cysteine, 0.4% BSA, 10% follicular fluid, 0.5 μg/mL FSH, 0.5 μg/mL LH and 50 μg/mL gentamicin sulfate and thereafter in medium of the same composition but without hormones. After 42, 44, 46, 48 hours of culture the maturation of oocytes of all categories and age groups was assessed by the sign of their release of the first polar body. Results. It was shown that at least 42 hours of in vitro culture of pubertal pig oocytes are required to ensure a high level of nuclear maturation. The duration of the in vitro maturation was found to be 44-48 hours for pre-pubertal pigs. Oocytes surrounded by 1-2 layers of CC, when cultured for less than 48 hours, are inferior in nuclear maturation to oocytes with a more multilayered cumulus. The presence of GC (granulosa cells) around COC retards retards the progression of nuclear maturation when cultured for less than 42 hours in prepubertal and 44 hours in pubertal gilts. Oocytes from cycling pigs reach peak maturation earlier than those from non-cycling gilts and can be used in assisted reproductive technologies (ART). Conclusions. It was concluded that both morphology of the surrounding cumulus cells and physiologic status of COC donor animals should be considered when choosing the duration of pig oocytes culture for the purpose of their in vitro maturation.

Myeloperoxidase-mimetic nanozyme generates hypochlorous acid for phagosomal bacteria elimination

Fighting against intracellular bacteria that can evade antibiotics is a long-standing challenge. Inspired by the abundant production of hydrogen peroxide (H2O2) within phagosomes during phagocytosis of bacteria, we have devised a myeloperoxidase-like nanozyme capable of facilitating phagosomal reactive oxygen species (ROS) production within the phagosomal environment, while simultaneously enabling the intracellular delivery of antibiotics. These novel nanozymes, denoted as GEN-NPs, has been fabricated through the conjugation of gentamicin (GEN) onto ultrasmall vanadium oxide nanoparticles (NPs). Our results demonstrate that GEN-NPs exhibit superior efficiency in eradicating both intracellular and extracellular bacteria, surpassing free GEN or NPs alone. This enhanced bactericidal activity can be attributed to the bacteria targeting ability and synergistic effect of myeloperoxidase-like GEN-NPs, which catalyze the conversion of abundant H2O2 into bactericide hypochlorous acid (HClO) and ROS within phagosomes. Moreover, the superior therapeutic outcomes of GEN-NPs have been observed across multiple infection models, outperforming the combined effect of GEN and NPs. This study posits that myeloperoxidase-like nanozyme presents a versatile platform for the development of next-generation therapeutics targeting intracellular bacteria.

Potential induction of hyperkeratosis in rats' cervi by gentamicin via induction of oxidative stress, inflammation and apoptosis.

The present study aimed to identify the possible effect of gentamicin (GEN) in Rats' Cervi. Estradiol Valerate (EV) was used to induce cervical hyperkeratosis. GEN was administered in absence of EV. Serum and cervical GEN concentration were determined. Levels of malondialdehyde (MDA), total nitrites/nitrate (NOx), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), sirtuin type 1 (Sirt1) and nuclear factor (erythroid-derived 2)-like-2 factors (Nrf2) were measured in cervix tissue. Expression of BAX and Bcl2 were determined. Cervical histopathological examination was done. EV and GEN significantly increased MDA, NOx, TNF-α and BAX/Bcl2 ratio with decrease in GSH, Nrf2 and Sirt1 levels in cervical tissue. Histopathological picture of diffuse and marked hyperkeratosis was detected in EV and GEN groups. In conclusion, GEN-induced cervical hyperkeratosis via induction of oxidative stress, inflammation and apoptosis.

Multi-layer antibacterial polyester fabrics for infection management and moisture wicking in a textile-based biomaterial wound dressing

Antibacterial woven polyester fabrics are drawing much attention in the medical and textile industries because they can provide many health-promoting properties that prevent infection while providing a barrier to the external environment. In this work, we developed and investigated two different polyester fabrics to demonstrate the antibacterial, non-adhesive, and moisture wicking properties of a multicomponent wound dressing. Vertical wicking of a braided layer composed of Poly-l-lactide (PLLA) yarn of 4-deep-grooved (4DG) fibers was tested using porcine blood serum to mimic wound exudate viscosity. Bacterial inhibition of Pseudomonas putida was measured after exposure to gentamicin sulfate (GS)-incorporated PLLA skin-contact layers of two different shaped yarns. Poly-ethylene glycol (PEG) was added to the GS PLLA contact layer to further prevent non-specific cellular attachment. Results indicated vertical wicking of moisture at 0.88 mm/s. While a specific wicking rate for adequate wound moisture regulation has not been indicated in the literature due to wound and patient variability, we assert that rapid removal of excess fluid from the wound bed, as demonstrated by our fabric is an essential component for a comprehensive wound dressing. Antibacterial experiments showed that GS exhibited both bactericidal and bacteriostatic trends by killing bacteria and further inhibiting growth, respectively. The surface treatment of PEG on PLLA contact layers showed less cellular attachment, promoting non-adhesion during dressing changes. Ultimately, using woven polyester medical textiles in wound care allows for optimizing parameters, such as antimicrobial uptake/release and moisture wicking for personalized healing. The construct studied here may serve as a tunable platform for development of wound dressings with specific antibacterial, moisture, and tissue adhesion requirements.

Smart zwitterionic coatings with precise pH-responsive antibacterial functions for bone implants to combat bacterial infections.

Hydrophilic antifouling coatings based on zwitterionic polymers have been widely applied for the surface modification of bone implants to combat biofilm formation and reduce the likelihood of implant-related infections. However, their long-term effectiveness is significantly limited by the lack of effective and precise antibacterial activity. Here, a pH-responsive smart zwitterionic antibacterial coating (PSB/GS coating) was designed and robustly fabricated onto titanium-base bone implants by using a facile two-step method. First, dopamine (DA) and a poly(sulfobetaine methacrylate-co-dopamine methacrylamide) (PSBDA) copolymer were deposited on implants via mussel-inspired surface chemistry, resulting in a hydrophilic base coating with abundant catechol residues. Next, an amino-rich antibiotic, gentamicin sulfate (GS), was covalently linked to the coating through the formation of acid-sensitive Schiff base bonds between the amine groups of GS and the catechol residues present in both the zwitterionic polymer and the DA component. During the initial implantation period, the hydrophilic zwitterionic polymers demonstrated the desired anti-fouling properties that could effectively reduce protein and bacterial adhesion by over 90%. With time, the bacterial proliferation led to a decrease in the microenvironment pH value, resulting in the hydrolysis of the acid-sensitive Schiff base bonds, thereby releasing GS on demand and effectively enhancing the anti-biofilm properties of coatings. Benefiting from this synergistic antifouling and smart antibacterial activities, the PSB/GS coating exerted an excellent anti-infective activity in both in vivo preoperative and postoperative infection rat models. This proposed facile yet effective coating strategy is expected to provide a promising solution to combat bone implant-related infections.

High-concentration continuous local antibacterial perfusion therapy: safety and potential efficacy for acute and chronic periprosthetic knee joint infection.

Periprosthetic joint infections (PJIs) following total knee arthroplasty (TKA) are among the most challenging pathologies to manage. Recently, continuous local antibiotic perfusion (CLAP) therapy has been introduced for treating musculoskeletal infections in orthopedics. This study aimed to determine the outcomes and risks of CLAP therapy combined with conventional treatment for PJIs after TKA. We retrospectively evaluated 14 patients with PJIs. For acute PJIs, CLAP therapy was performed alongside debridement, intravenous antibiotics, and implant retention. For chronic PJIs, a two-stage revision with CLAP therapy and intravenous antibiotics was performed. Implants were replaced with a cement mold incorporating CLAP therapy, followed by revision surgery after 3 months. For all patients, 120mg/day of gentamicin (GM) was locally administered into the knee joint for 2 weeks as part of CLAP therapy, in combination with perioperative intravenous antibiotics. Five patients developed acute PJIs, and nine developed chronic PJIs after TKA. The mean follow-up period was 18.4 (15.2-21.1) months. All five patients with PJIs treated with one-stage surgery (debridement and insert exchange only) successfully preserved their implants. Among the nine patients with chronic PJIs, seven underwent CLAP therapy combined with two-stage revision surgery, resulting in successful treatment without relapse, whereas the remaining two patients were initially treated with one-stage surgery and CLAP therapy but failed to retain their implants, and subsequently required additional two-stage revision surgery, which ultimately succeeded. No adverse effects from GM were reported. Our results suggest that CLAP therapy is safe and may be effective for treating acute and most chronic PJIs after TKA.

Investigating Antibiotic Effects on Trichoderma sp. Growth and Virulence: A Basis for CRISPR-Cas9 Preparation

Trichoderma sp. is an antagonistic fungus that is used as a biological control. Understanding how antibiotics affect Trichoderma sp. growth and virulence is critical for developing effective CRISPR-Cas9 gene editing strategies. However, implementing CRISPR-Cas9 technology in Trichoderma requires a comprehensive understanding of how external factors, such as antibiotic exposure, affect the fungus’s growth and virulence over successive generations. Antibiotics long-term effects on fungal physiology remain unclear. This study addresses this gap by evaluating the impact of antibiotic treatment on Trichoderma sp., laying the groundwork for effective and precise genetic modifications using CRISPR-Cas9. Five types of antibiotics used for this test are Chloramphenicol, Gentamicin sulphate, Kanamycin Meiji, Penicillin Meiji, and Tetracycline HCI. The study found that several antibiotics accelerated the growth of Trichoderma sp., allowing the fungus to fill a petri dish in under 5 days. However, this rapid growth was delayed in subcultures over five generations. Although the color of the fungus did not vary much across treatments, subtle changes in density and brightness were detected in each generation using the "color grab" application, with these attributes diminishing over time. Spore density in the fourth generation, particularly under chloramphenicol and gentamicin treatments, differed from other antibiotics. Germination rates were initially high (≥70%) but decreased with each generation. The fungus maintained strong virulence against Fusarium sp., with inhibition rates ≥50%, and exhibited mycoparasitism, characterized by hyphal growth at the Fusarium sp. colony edges. This research contributes to understanding how antibiotic exposure affects the long-term growth, spore density, and virulence of Trichoderma sp., providing essential insights for optimizing its use in biocontrol and genetic engineering applications.

Multidrug Resistant Enteric Bacteria from Cancer Patients Admitted in Douala Laquintinie Hospital, Littoral Region of Cameroon.

Patients with cancer have weakened immune systems, making them more vulnerable to infections. This study was carried out to determine the bacterial origins of enteric disorders in cancer patients and noncancer patients at the Oncology Department of Laquintinie Hospital in Douala. A cross-sectional study was conducted from October 2021 to March 2023. Stool samples from 307 cancer patients with enteric disorders and 200 noncancer patients with enteric disorders were examined to diagnose the presence of bacteria using various techniques. Among all participants in this study, 62.13% were female and 37.87% were male. The average age of the participants was 46.38 ± 15.81 years, with a minimum age of 10 years and a maximum age of 84 years. The average age of participants was significantly higher (p < 0.000) in cancer patients (49.54 ± 14.65 years) compared to noncancer patients (41.53 ± 16.33 years). Proteus mirabilis, Proteus vulgaris, Salmonella typhi, Enterobacter cloacae, Klebsiella pneumoniae, Yersinia intemedia, and Klebsiella oxytoca were more frequently isolated in cancer patients than in noncancer patients, with the respective percentages of 56.25% versus 43.75%, 50.00% versus 50.00%, 61.66% versus 38.34%, 66.66% versus 33.34%, 72.22% versus 27.78%, 80.00 versus 20.00%, and 100% versus 0.00%. Most isolates were sensitive to imipenem (IMP), gentamicin (GEN), and amikacin (AMK). Proteus vulgaris, the most prevalent isolate, showed significantly high resistance (with p < 0.05) in cancer patients compared to noncancer patients at amoxicillin/clavuranic acid (AMC) (89.13% versus 41.30%), ceftriaxone (CTR) (63.04% versus 39.13%), ciprofloxacin (CIP) (65.22% versus 34.18%), and tetracycline (TET) (93.48% versus 63.04%). Multidrug resistance was observed in cancer patients compared to noncancer patients for Klebsiella pneumoniae (85.00% versus 60.00%), Salmonella typhi (84.62% versus 60.00%), and Klebsiella oxytoca (86.49% versus 43.48%). The increase in the number of Gram-negative infections among cancer patients, as shown in the present study, highlights the need for broad-spectrum therapy and effective planning of control programs to reduce bacterial diseases among cancer patients.

Simultaneous Estimation of Curcumin and Gentamicin by UV-VIS Spectrometric Methods or Derivative Spectroscopic Techniques

A simultaneous study is very important analytical parameter which helps to assess compatibility of mixture of drugs. UV spectrophotometer is one of the simplest and efficient methods to assess simultaneous parameters. Due to its economical approach, we have used UV spectrophotometer. Curcumin and Gentamicin sulphate have zero crossing points of 420 nm and 244 nm, respectively, in first-order derivative spectroscopy. The solvent for the spectrophotometric process was 0.1 N NaOH. Curcumin and Gentamicin sulphate linearity was established over range of concentrations of 2–12 g/ml, with correlation coefficients of 0.995 and 0.993. The mean percent recoveries Curcumin and Gentamicin sulphate were found to be in the range of 98.88 percent and 98.54 percent, respectively. The approach has been found to be repeatable in both inter day and intraday testing. The approach was proven to be both precise and reliable. According to the recovery investigation, the approach was effectively applied to pharmaceutical formulation with no interference from excipients. The results of the analysis were statistically evaluated, as well as by recovery trials. The LOD and LOQ for Gentamicin sulphate in phosphate buffer were found to be 0.024µg/ml and 0.045µg/ml, respectively and values for Curcumin were 0.024µg/ml and 0.037 µg/ml, respectively which indicates adequate sensitivity of method

Extremely low friction coefficient and mechanically robust photonic film towards antibiotic drug release

Excessive friction between hydrogels and biological tissue is a major risk factor that can lead to tissue damage and inflammation, limiting their application as biomaterials. Herein, we designed a photonic hydrogel film with an extremely low friction coefficient (COF∼1.71 × 10−3) by embedding free linear polyacrylamide (PAAm) polymer chains within a thermosensitive hydrogel matrix. This photonic hydrogel with brush structure possesses elastic deformation and reversible color change due to its excellent mechanical property. As proof-of-concept, gentamicin sulfate (GS) was selected as model of antibiotic drug, the structural color of material changes during the release of GS. Consequently, the cumulative release amount of the GS can be evaluated by measuring the reflection wavelength. These features make our strategy potentially useful in preparation of materials with low COF and extending the application of photonic hydrogels, including ocular drug delivery and monitoring systems, as well as articular tissue-mechanical sensors.

Muscle-Derived Stem/Progenitor Cells Ameliorate Acute Kidney Injury in Rats through the Anti-Apoptotic Pathway and Demonstrate Comparable Effects to Bone Marrow Mesenchymal Stem Cells.

Background and Objectives: To date, the therapeutic potential of skeletal muscle-derived stem/progenitor cells (MDSPCs) for acute kidney injury (AKI) has only been evaluated by our research group. We aimed to compare MDSPCs with bone marrow mesenchymal stem cells (BM-MSCs) and evaluate their feasibility for the treatment of AKI. Materials and Methods: Rats were randomly assigned to four study groups: control, GM (gentamicin) group, GM+MDSPCs, and GM+BM-MSCs. AKI was induced by gentamicin (80 mg/kg/day; i.p.) for 7 consecutive days. MDSPCs and BM-MSCs were injected 24 h after the last gentamicin injection. Kidney parameters were determined on days 0, 8, 14, 21, and 35. Results: MDSPCs and BM-MSCs accelerated functional kidney recovery, as reflected by significantly lower serum creatinine levels and renal injury score, higher urinary creatinine and creatinine clearance levels (p < 0.05), lower TUNEL-positive cell number, and decreased KIM-1 and NGAL secretion in comparison to the non-treated AKI group. There was no significant difference in any parameters between the MDSPCs and BM-MSCs groups (p > 0.05). Conclusions: MDSPCs and BM-MSCs can migrate and incorporate into injured renal tissue, resulting in a beneficial impact on functional and morphological kidney recovery, which is likely mediated by the secretion of paracrine factors and an anti-apoptotic effect. MDSPCs were found to be non-inferior to BM-MSCs and therefore can be considered as a potential candidate strategy for the treatment of AKI.

Morphology, Cytotoxicity, and Antimicrobial Activity of Electrospun Polycaprolactone Biomembranes with Gentamicin and Nano-Hydroxyapatite.

The aim of this research is to develop new nanocomposite membranes (NMs) for guided bone regeneration from polycaprolactone (PCL), with different concentrations of gentamicin sulfate (GEN) and nano-hydroxyapatite (nHAP) through electrospinning. The obtained NMs were characterized for structure through SEM and AFM, which revealed the influence of GEN and nHAP on the fiber diameter. The addition of GEN lowered the fiber diameter, and the addition of nHAP increased the diameter of the fibers. The NMs demonstrated antibacterial properties against P. aeruginosa, S. aureus, B. cereus, and E. coli depending on the drug concentration, while being negligibly affected by the nHAP content. NM cytotoxicity assessment, performed once using the MTT assay, revealed no cytotoxicity. The developed NMs could be a promising alternative for guided bone regeneration.

DNase aggravates intestinal microvascular injury in IBD patients by releasing NET-related proteins.

Neutrophils accumulate in the inflammatory mucosa of patients with inflammatory bowel disease (IBD), and excessive release of NETs (neutrophil extracellular traps may be one of the important factors that cause IBD progression. However, the specific mechanism underlying vascular injury caused by NETs remains unclear. Immunofluorescence, ELISA, and flow cytometry were used in this study to detect the expression of NETs and DNase in the tissue and peripheral blood samples of patients with IBD. DSS mouse model was used to detect colon injury and vascular permeability. We found that NETs and DNase levels increased in the colon of patients with IBD. We found an increase in the activity of NET-related MPO released by DNase. DNase released NET-related proteins and damaged vascular endothelial cells invitro. In DSS mouse model, the synchronous increase of DNase and NETs in the colon leads to an increase in vascular injury markers (CD44, sTM). DNase aggravated colon injury and increased vascular permeability invivo, which was inhibited by gentamicin sulfate (GS). GS does not reduce the expression of DNase, but rather reduces the release of NET-related proteins to protect vascular endothelium by inhibiting DNase activity. MPO and histones synergistically damaged the vascular endothelium, and vascular injury can be improved by their active inhibitors. We further found that H2 O2 is an important substrate for MPO induced vascular damage. In conclusion, in IBD, DNase, and NET levels increased synchronously in the lesion area and released NET-related proteins to damage the vascular endothelium. Therefore, targeting DNase may be beneficial for the treatment of IBD.

Protective impacts of Artemisia annua against hepatic toxicity induced by gentamicin.

The current study aimed to investigate the ameliorative effects of Artemisia annua (RA) extract on hepatic toxicity induced by gentamicin injection mice. Sixteen mice were divided into four groups; the control group received saline, the second group received 1% A. annua (RA) extract, third group injected 80mg/kg gentamicin (GEN) intraperitoneally. The protective group treated with a combination of GEN and A. annua. All mice were treated for consecutive 15days. Results confirmed that hepatic biomarkers (GPT, GCT, GOT, IL-6 and IL-1β), all were altered after gentamycin injection. The histological analysis confirmed that gentamycin injected mice showed portal vein congestion, micro and macro steatosis, and nuclear pyknosis of hepatocytes. The protective group showed intact central vein with less microsteatosis of some hepatocytes. Immunochemistry analysis confirmed that the immunoreactivity of COX-2 gene showed negative impact in examined groups. Unlike, NF-κB gene exhibited diffuse positive expression in the gentamicin group. TGF-β1 immunoreactivity was mild positive in control and highly upregulated in gentamicin treated mice, all were normalized after RA administration. In conclusion, RA showed a beneficial impact against gentamycin induced hepatic toxicity at cellular and biochemical levels by regulating proteins and inflammatory markers associated with liver activity.