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Molecules (Basel, Switzerland) Jun 2024(1) Background: GHaK is derived from the antimicrobial peptide temporin-GHa by substituting the amino acid H with K to enhance its bactericidal activity. The present...
(1) Background: GHaK is derived from the antimicrobial peptide temporin-GHa by substituting the amino acid H with K to enhance its bactericidal activity. The present research aims to broaden the pharmacological potential of GHaK by exploring its antineoplastic activity against human lung adenocarcinoma. (2) Methods: The cell viability, migration, invasion, apoptosis, and cell cycle of A549 and PC-9 cells were tested after GHaK treatment. miRNA sequencing, RT-PCR, Western blotting, and luciferase reporter gene assay were further performed to reveal the potential mechanism. (3) Results: GHaK significantly suppressed cell viability, migration, and invasion; induced apoptosis; and caused cell cycle arrest in the G2/M and S phase in PC-9 and A549 cells, respectively. The miRNA sequencing results show a total of 161 up-regulated and 115 down-regulated miRNAs. Furthermore, the study identified six up-regulated miRNAs (miR-4516, miR-4284, miR-204-5p, miR-12136, miR-4463, and miR-1296-3p) and their inhibitory effects on the expressions of target genes (Wnt 8B, FZD2, DVL3, and FOSL1) caused by miR-4516 directly interacting with Wnt 8B. Western blotting revealed the down-regulation of p-GSK-3β, along with a decreased expressions of cyclin A1 and CDK2 in A549 cells and cyclin B1 and CDK1 in PC-9 cells. (4) Conclusions: Temporin-GHaK exhibits antineoplastic activity against human lung adenocarcinoma by inhibiting the Wnt signaling pathway through miRNA-4516.
Topics: Humans; MicroRNAs; Wnt Signaling Pathway; Adenocarcinoma of Lung; Antineoplastic Agents; Lung Neoplasms; Gene Expression Regulation, Neoplastic; Apoptosis; Cell Line, Tumor; Cell Movement; A549 Cells; Cell Proliferation; Cell Survival; Antimicrobial Cationic Peptides
PubMed: 38930863
DOI: 10.3390/molecules29122797 -
Molecules (Basel, Switzerland) Jun 2024The current article reports the investigation of three new Ni(II) complexes with -donor dithiocarbazate ligands: [Ni(L)PPh] (), [Ni(L)PPh] (), and [Ni(L)Py] ()....
The current article reports the investigation of three new Ni(II) complexes with -donor dithiocarbazate ligands: [Ni(L)PPh] (), [Ni(L)PPh] (), and [Ni(L)Py] (). Single-crystal X-ray analyses revealed mononuclear complexes with a distorted square planar geometry and the metal centers coordinated with a doubly deprotonated dithiocarbazate ligand and coligand pyridine or triphenylphosphine. The non-covalent interactions were investigated by the Hirshfeld surface and the results revealed that the strongest interactions were π⋅⋅⋅π stacking interactions and non-classical hydrogen bonds C-H···H and C-H···N. Physicochemical and spectroscopic methods indicate the same structures in the solid state and solution. The toxicity effects of the free ligands and Ni(II) complexes were tested on the human breast cancer cell line MCF-7 and non-malignant breast epithelial cell line MCF-10A. The half-maximal inhibitory concentration (IC) values, indicating that the compounds were potent in inhibiting cell growth, were obtained for both cell lines at three distinct time points. While inhibitory effects were evident in both malignant and non-malignant cells, all three complexes demonstrated lower IC values for malignant breast cell lines than their non-malignant counterparts, suggesting a stronger impact on cancerous cell lines. Furthermore, molecular docking studies were performed showing the complex () as a promising candidate for further therapeutic exploration.
Topics: Humans; Nickel; Molecular Docking Simulation; Antineoplastic Agents; Ligands; Coordination Complexes; Cell Line, Tumor; Crystallography, X-Ray; MCF-7 Cells; Molecular Structure; Cell Proliferation; Drug Design
PubMed: 38930825
DOI: 10.3390/molecules29122759 -
Microorganisms Jun 2024is the first reported pathogen within the genus to cause a catheter-related bloodstream infection, which occurred in 2015. In this study, the complete genome assembly...
is the first reported pathogen within the genus to cause a catheter-related bloodstream infection, which occurred in 2015. In this study, the complete genome assembly of was constructed, and the complete genome of FBCC-B549 consists of a single chromosome (3,137,745 bp) without plasmids. The constructed genome of was compared with those of two closely related species within the genus. exhibited a pattern similar to in terms of gene clusters and synteny analysis. Contrary to previous studies, biosynthetic gene cluster (BGC) analysis for predicting secondary metabolites revealed the presence of the LAP biosynthesis pathway in the complete genome of , predicting the potential synthesis of the secondary metabolite plantazolicin. Furthermore, an analysis to investigate the potential pathogenicity of did not reveal any antibiotic resistance genes; however, nine virulence factors were identified in the Virulence Factor Database (VFDB). According to these matching results in the VFDB, despite identifying a few factors involved in biofilm formation, further research is required to determine the actual impact of on pathogenicity. The complete genome of is expected to serve as a valuable resource for future studies on , which currently lack sufficient genomic sequence information.
PubMed: 38930609
DOI: 10.3390/microorganisms12061227 -
Microorganisms Jun 2024SARS-CoV-2, the pathogen causing COVID-19, continues to pose a significant threat to public health and has had major economic implications. Developing safe and effective...
SARS-CoV-2, the pathogen causing COVID-19, continues to pose a significant threat to public health and has had major economic implications. Developing safe and effective vaccines and therapies offers a path forward for overcoming the COVID-19 pandemic. The presented study, performed by using the informational spectrum method (ISM), representing an electronic biology-based tool for analysis of protein-protein interactions, identified the highly conserved region of spike protein (SP) from SARS-CoV-2 virus, which is essential for recognition and targeting between the virus and its protein interactors on the target cells. This domain is suggested as a promising target for the drug therapy and vaccines, which could be effective against all currently circulating variants of SARS-CoV-2 viruses. The analysis of the virus/host interaction, performed by the ISM, also revealed OX-2 membrane glycoprotein (CD200) as a possible interactor of SP, which could serve as a novel therapeutic target for COVID-19 disease.
PubMed: 38930566
DOI: 10.3390/microorganisms12061185 -
Microorganisms Jun 2024We determined antibiotic susceptibility and employed Oxford Nanopore whole-genome sequencing to explore strain diversity, resistance, and virulence gene carriage among...
We determined antibiotic susceptibility and employed Oxford Nanopore whole-genome sequencing to explore strain diversity, resistance, and virulence gene carriage among methicillin-resistant (MRSA) strains from different infection sites and timepoints in a tertiary Kenyan hospital. Ninety-six nonduplicate clinical isolates recovered between 2010 and 2023, identified and tested for antibiotic susceptibility on the VITEK ID/AST platform, were sequenced. Molecular typing, antibiotic resistance, and virulence determinant screening were performed using the relevant bioinformatics tools. The strains, alongside those from previous studies, were stratified into two periods covering 2010-2017 and 2018-2023 and comparisons were made. Mirroring phenotypic profiles, '″ [aminoglycosides]; (S84L) and (S80Y) [fluoroquinolones]; [anti-folates]; and [tetracycline] resistance determinants dominated the collection. While the proportion of ST239/241-t037-SCCmec III among MRSA reduced from 37.7% to 0% over the investigated period, ST4803-t1476-SCCmec IV and ST152-t355-SCCmec IV were pre-eminent. The prevalence of Panton-Valentine leucocidin (PVL) and arginine catabolic mobile element (ACME) genes was 38% (33/87) and 6.8% (6/87), respectively. We observed the displacement of HA-MRSA ST239/241-t037-SCCmec III with the emergence of ST152-t355-SCCmec IV and a greater clonal heterogeneity. The occurrence of PVL+/ACME+ CA-MRSA in recent years warrants further investigations into their role in the CA-MRSA virulence landscape, in a setting of high PVL prevalence.
PubMed: 38930553
DOI: 10.3390/microorganisms12061171 -
Microorganisms May 2024The endometrium remains a difficult tissue for the analysis of microbiota, mainly due to the low bacterial presence and the sampling procedures. Among its pathologies,...
BACKGROUND
The endometrium remains a difficult tissue for the analysis of microbiota, mainly due to the low bacterial presence and the sampling procedures. Among its pathologies, endometrial cancer has not yet been completely investigated for its relationship with microbiota composition. In this work, we report on possible correlations between endometrial microbiota dysbiosis and endometrial cancer.
METHODS
Women with endometrial cancer at various stages of tumor progression were enrolled together with women with a benign polymyomatous uterus as the control. Analyses were performed using biopsies collected at two specific endometrial sites during the surgery. This study adopted two approaches: the absolute quantification of the bacterial load, using droplet digital PCR (ddPCR), and the analysis of the bacterial composition, using a deep metabarcoding NGS procedure.
RESULTS
ddPCR provided the first-ever assessment of the absolute quantification of bacterial DNA in the endometrium, confirming a generally low microbial abundance. Metabarcoding analysis revealed a different microbiota distribution in the two endometrial sites, regardless of pathology, accompanied by an overall higher prevalence of pathogenic bacterial genera in cancerous tissues.
CONCLUSIONS
These results pave the way for future studies aimed at identifying potential biomarkers and gaining a deeper understanding of the role of bacteria associated with tumors.
PubMed: 38930472
DOI: 10.3390/microorganisms12061090 -
Journal of Clinical Medicine Jun 2024(1) This research aimed to evaluate the changes in ganglion cell layer thickness (GCLT) after uncomplicated cataract surgery in patients without previous ocular...
(1) This research aimed to evaluate the changes in ganglion cell layer thickness (GCLT) after uncomplicated cataract surgery in patients without previous ocular pathology and the impact of the appearance of cystoid macular edema on the GCLT and visual acuity. (2) The evaluation of 174 patients was performed with the indication of uncomplicated cataract surgery. The variables analyzed were demographic data, best-corrected visual acuity (BCVA), cataract type and OCT (Optical Coherence Tomography) measurements of central macular thickness (CMT), and the presence of cysts and GCLT preoperatively and one day, one and three months after surgery. (3) There was a relationship between the postoperative increase in retinal GCLT and BCVA after uncomplicated cataract surgery. The presence of microcysts reduced the thickness of the GCL, which is significantly related to the loss of BCVA. The appearance of cystoid macular edema one month after surgery was also related to the preoperative CMT. There was a statistically significant decrease in preoperative GCL but a statistically significant increase in preoperative CMT in patients with microcysts one-month post-surgery. (4) There is a relationship between postoperative retinal GCLT and BCVA after uncomplicated cataract surgery. The presence of microcysts significantly reduces the thickness of the GCL, which is significantly related to the loss of BCVA.
PubMed: 38930108
DOI: 10.3390/jcm13123579 -
Journal of Clinical Medicine Jun 2024: Lumbar disc herniation, a complex challenge in spinal health, significantly impacts individuals across diverse age groups. This article delves into the intricacies of...
: Lumbar disc herniation, a complex challenge in spinal health, significantly impacts individuals across diverse age groups. This article delves into the intricacies of this condition, emphasising the pivotal role of anatomical considerations in its understanding and management. Additionally, lumbar discectomy might be considered an "easy" surgery; nevertheless, it carries significant risks. The aim of the study was to present a groundbreaking "three-step approach" with some anatomical insight derived from our comprehensive clinical experiences, designed to systematise the surgical approach and optimise the outcomes, especially for young spine surgeons. We highlighted the purpose of the study and introduced our research question(s) and the context surrounding them. : This retrospective study involved patients treated for lumbar disc herniation at a single institution. The patient demographics, surgical details, and postoperative assessments were meticulously recorded. All surgeries were performed by a consistent surgical team. : A total of 847 patients of the 998 patients initially included completed the follow-up period. A three-step approach was performed for every patient. The recurrence rate was 1.89%. Furthermore, the incidence of lumbar instability and the need for reoperation were carefully examined, presenting a holistic view of the outcomes. : The three-step approach emerged as a robust and effective strategy for addressing lumbar disc herniation. This structured approach ensures a safe and educational experience for young spinal surgeons.
PubMed: 38930100
DOI: 10.3390/jcm13123571 -
Journal of Clinical Medicine Jun 2024: Endoscopic submucosal dissection is a minimally invasive endoscopic procedure for the removal of neoplastic benign and early malignant lesions in the gastrointestinal...
: Endoscopic submucosal dissection is a minimally invasive endoscopic procedure for the removal of neoplastic benign and early malignant lesions in the gastrointestinal tract. In this study, we analyse the success and safety of rectal ESD at Linz hospitals, focusing on a specific endoscopist. Additionally, we examine whether there is a learning curve regarding success parameters. : This retrospective study included all 102 patients who underwent endoscopic submucosal dissection of the rectum by a defined endoscopist at Ordensklinikum Hospital and Kepler University Hospital between December 2010 and May 2021. With the collected data, a descriptive statistic was carried out and regression analyses were performed. : The en bloc resection rate was 78.4% and the rate of lesions removed in healthy tissue was 55.6%. The average procedure time was 179 min and the complication rate was 7.8%. In total, 26.4% of cases showed carcinoma; in 25.9% of these cases, an oncologically curative resection was achieved with ESD. Follow-up data were available for 61.1% of cases, with recurrence being diagnosed in 3.6% of cases. A learning curve was observed regarding the rate of lesions removed in healthy tissue and the procedure time, but not regarding the en bloc resection rate. : Endoscopic submucosal dissection is a safe method for the removal of large rectal adenomas and early carcinomas. The en bloc resection rate of the analysed procedures is within the range of comparable European studies. The rate of lesions removed in healthy tissue is below the R0 resection rate of the comparative literature; however, a learning curve could be observed in this parameter.
PubMed: 38930059
DOI: 10.3390/jcm13123530 -
Journal of Clinical Medicine Jun 2024: Leiomyosarcoma (LMS) originating from the adrenal gland is exceedingly rare, constituting a minute fraction of soft tissue sarcomas. Due to its rarity, with less than... (Review)
Review
: Leiomyosarcoma (LMS) originating from the adrenal gland is exceedingly rare, constituting a minute fraction of soft tissue sarcomas. Due to its rarity, with less than 50 documented cases in English medical literature, the diagnosis and management of adrenal LMS remain challenging. The aim of this study was to perform a review of the literature, in order to evaluate the prognosis of these rare cancers and report our specific case. : A systematic review of the literature was conducted using PubMed, Web of Science, Google Scholar, and Scopus databases, up to December 2020. The search utilized MeSH terms such as "Adrenal Gland Neoplasms," "Leiomyosarcoma," "Adrenalectomy," and "Smooth Muscle Tumor." The inclusion criteria focused on studies reporting patients with a histopathological diagnosis of adrenal leiomyosarcoma. The PRISMA guidelines were followed to ensure a comprehensive analysis. : Out of 63 identified studies, 43 met the inclusion criteria and were reviewed. These studies highlighted the rarity and aggressive behavior of adrenal leiomyosarcoma. Surgical excision remains the cornerstone of treatment, often complemented by adjuvant therapies. The reviewed case involved a 52-year-old woman who underwent a right laparoscopic adrenalectomy for a 9 × 7 × 6 cm grade 3 leiomyosarcoma. Despite subsequent adjuvant chemotherapy, hepatic metastases were detected, illustrating the aggressive nature of the disease. The literature underscores the importance of histopathological analysis and long-term surveillance for managing disease progression. : Optimal management of adrenal leiomyosarcoma requires a multidisciplinary approach and meticulous follow-up. The rarity of the disease poses challenges for standardizing treatment, but surgical excision and tailored adjuvant therapies show promise. Further research is essential to refine treatment strategies and improve prognosis for this rare malignancy.
PubMed: 38930027
DOI: 10.3390/jcm13123499