Explore the vast range of titles available.

Bacterial and fungal biofilm has increased antibiotic resistance and plays an essential role in many persistent diseases. Biofilm-associated chronic infections are difficult to treat and reduce the efficacy of medical devices. This global problem has prompted extensive research to find alternative strategies to fight microbial chronic infections. Plant bioactive metabolites with antibiofilm activity are known to be potential resources to alleviate this problem. The phytochemical screening of some medicinal plants showed different active groups, such as stilbenes, tannins, alkaloids, terpenes, polyphenolics, flavonoids, lignans, quinones, and coumarins. Synergistic effects can be observed in the interaction between plant compounds and conventional drugs. This review analyses and summarises the current knowledge on the synergistic effects of plant metabolites in combination with conventional antimicrobials against biofilms of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. The synergism of conventional antimicrobials with plant compounds can modify and inhibit the mechanisms of acquired resistance, reduce undesirable effects, and obtain an appropriate therapeutic effect at lower doses. A deeper knowledge of these combinations and of their possible antibiofilm targets is needed to develop next-generation novel antimicrobials and/or improve current antimicrobials to fight drug-resistant infections attributed to biofilm.

Probiotic therapy needs consideration as an alternative strategy to prevent and possibly treat corneal infection. This study aimed to assess the preventive effect of Lactobacillus reuteri and Bifidobacterium longum subsp. infantis on reducing the infection of human corneal epithelial (HCE) cells caused by Pseudomonas aeruginosa. The probiotics’ preventive effect against infection was evaluated in cell monolayers pretreated with each probiotic 1 h and 24 h prior to P. aeruginosa challenge followed by 1 h and 24 h of growth in combination. Cell adhesion, cytotoxicity, anti-inflammatory, and antinitrosative activities were evaluated. L. reuteri and B. longum adhered to HCE cells, preserved occludin tight junctions’ integrity, and increased mucin production on a SkinEthicTM HCE model. Pretreatment with L. reuteri or B. longum significantly protected HCE cells from infection at 24 h, increasing cell viability at 110% (110.51 ± 5.15; p ≤ 0.05) and 137% (137.55 ± 11.97; p ≤ 0.05), respectively. Each probiotic showed anti-inflammatory and antinitrosative activities, reducing TNF-α level (p ≤ 0.001) and NOx amount (p ≤ 0.001) and reestablishing IL-10 level (p ≤ 0.001). In conclusion, this study demonstrated that L. reuteri and B. longum exert protective effects in the context of corneal infection caused by P. aeruginosa by restoring cell viability and modulating inflammatory cytokine release.

The term “inflammatory bowel disease” (IBD) describes a class of relapse-remitting conditions that affect the gastrointestinal (GI) tract. Among these, Crohn’s disease (CD) and ulcerative colitis (UC) are two of the most globally prevalent and debilitating conditions. Several articles have brought attention to the significant role that inflammation and oxidative stress cooperatively play in the development of IBD, offering a different viewpoint both on its etiopathogenesis and on strategies for the effective treatment of these conditions. Marine ecosystems may be a significant source of physiologically active substances, supporting the search for new potential clinical therapeutics. Based on this evidence, this review aims to comprehensively evaluate the activity of marine algae and deriving biomolecules in decreasing pathological features of CD and UC. To match this purpose, a deep search of the literature on PubMed (MEDLINE) and Google Scholar was performed to highlight primary biological mechanisms, the modulation of inflammatory and oxidative stress biochemical parameters, and potential clinical benefits deriving from marine species. From our findings, both macroalgae and microalgae have shown potential as therapeutic solutions for IBD due to their bioactive compounds and their anti-inflammatory and antioxidant activities which are capable of modulating markers such as cytokines, the NF-κB pathway, reactive oxidative and nitrosative species (ROS and RNS), trefoil factor 3 (TFF3), lactoferrin, SIRT1, etc. However, while we found promising preclinical evidence, more extensive and long-term clinical studies are necessary to establish the efficacy and safety of marine algae for IBD treatment.

Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic nigrostriatal neurons, which causes disabling motor disorders. Scientific findings support the role of epigenetics mechanism in the development and progression of many neurodegenerative diseases, including PD. In this field, some studies highlighted an upregulation of Enhancer of zeste homolog 2 (EZH2) in the brains of PD patients, indicating the possible pathogenic role of this methyltransferase in PD. The aim of this study was to evaluate the neuroprotective effects of GSK-343, an EZH2 inhibitor, in an in vivo model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic degeneration. Specifically, nigrostriatal degeneration was induced by MPTP intraperitoneal injection. GSK-343 was administered intraperitoneally daily at doses of 1 mg/kg, 5 mg/kg and 10 mg/kg, mice were killed 7 days after MPTP injection. Our results demonstrated that GSK-343 treatment significantly improved behavioral deficits and reduced the alteration of PD hallmarks. Furthermore, GSK-343 administration significantly attenuated the neuroinflammatory state through the modulation of canonical and non-canonical NF-κB/IκBα pathway as well as the cytokines expression and glia activation, also reducing the apoptosis process. In conclusion, the obtained results provide further evidence that epigenetic mechanisms play a pathogenic role in PD demonstrating that the inhibition of EZH2, mediated by GSK-343, could be considered a valuable pharmacological strategy for PD.

Bacterial vaginosis (BV) is a common vaginal dysbiosis characterized by a malodorous discharge and irritation. The imbalance of the vaginal microbiota plays a key role in the development of BV . It has been demonstrated that Gardnerella vaginalis (GV), a facultative anaerobic bacillus, is involved in BV. Due to the rising number of antimicrobial-resistant species, recurrence of BV is becoming more frequent in women; thus, alternative treatments to antibiotics are needed. Natural substances have recently shown a great efficacy for the treatment of vaginal dysbiosis. Thus, this study aimed to investigate the beneficial effect of a product containing pea protein (PP), grape seed extract (GS) and lactic acid (LA) in an in vivo model of Gardnerella vaginalis-induced vaginosis by intravaginal administration of GV suspension (1 × 10 6  CFU/20 µL saline). Our results demonstrated that the product containing PP, GS and LA significantly reduced GV proliferation. More specifically, it significantly preserved tissue architecture and reduced neutrophil infiltration, inflammatory markers and sialidase activity when used both as a pre- or a post-treatment. Moreover, the product displayed strong bioadhesive properties. Therefore, our data suggested that the product containing PP, GS and LA could be used as alternative preventive or curative treatment for the management of BV.

Acyl CoA binding protein encoded by diazepam binding inhibitor (ACBP/DBI) is a tissue hormone that stimulates lipo-anabolic responses and inhibits autophagy, thus contributing to aging and age-related diseases. Protein expression profiling of ACBP/DBI was performed on mouse tissues to identify organs in which this major tissue hormone is expressed. Transcriptomic and proteomic data bases corroborated a high level of human-mouse interspecies conservation of ACBP/DBI expression in different organs. Single-cell RNA-seq data confirmed that ACBP/DBI was strongly expressed by parenchymatous cells from specific human and mouse organs (e.g., kidney, large intestine, liver, lung) as well as by myeloid or glial cells from other organs (e.g., adipose tissue, brain, eye) following a pattern that was conserved among the two species. We identified a panel of 44 mRNAs that are strongly co-expressed with ACBP/DBI mRNA in normal and malignant human and normal mouse tissues. Of note, 22 (50%) of these co-expressed mRNAs encode proteins localized at mitochondria, and mRNAs with metabolism-related functions are strongly overrepresented (66%). Systematic data mining was performed to identify transcription factors that regulate ACBP/DBI expression in human and mouse. Several transcription factors, including growth response 1 (EGR1), E2F Transcription Factor 1 (E2F1, which interacts with retinoblastoma, RB) and transformation-related protein 53 (TRP53, best known as p53), which are endowed with oncosuppressive effects, consistently repress ACBP/DBI expression as well as its co-expressed mRNAs across multiple datasets, suggesting a mechanistic basis for a coregulation network. Furthermore, we identified multiple transcription factors that transactivate ACBP/DBI gene expression together with its coregulation network. Altogether, this study indicates the existence of conserved mechanisms determining the expression of ACBP/DBI in specific cell types of the mammalian organism.

The gut–brain axis (GBA) refers to the biochemical bidirectional communication between the central nervous system (CNS) and the gastrointestinal tract, linking brain and gut functions. It comprises a complex network of interactions involving the endocrine, immune, autonomic, and enteric nervous systems. The balance of this bidirectional pathway depends on the composition of the gut microbiome and its metabolites. While the causes of neurodegenerative diseases (NDDs) vary, the gut microbiome plays a crucial role in their development and prognosis. NDDs are often associated with an inflammation-related gut microbiome. However, restoring balance to the gut microbiome and reducing inflammation may have therapeutic benefits. In particular, introducing short-chain fatty acid-producing bacteria, key metabolites that support gut homeostasis, can help counteract the inflammatory microbiome. This strong pathological link between the gut and NDDs underscores the gut–brain axis (GBA) as a promising target for therapeutic intervention. This review, by scrutinizing the more recent original research articles published in PubMed (MEDLINE) database, emphasizes the emerging notion that GBA is an equally important pathological marker for neurological movement disorders, particularly in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease and neurotraumatic disorders such as traumatic brain injury and spinal cord injury. Additionally, the GBA presents a promising therapeutic target for managing these diseases.

Oral squamous cell carcinoma (OSCC) is one of the most common human malignancies worldwide. The molecular mechanisms of OSCC pathogenesis are still unknown; however, in recent years, several reports have focused on the role of enhancer of zeste homolog 2 (EZH2) in OSCC. Therefore, in this study we aimed to investigate the effects of GSK343, a selective EZH2 inhibitor, and its impact on the signaling pathways in OSCC, using an in vitro and in vivo orthotopic model. In the in vitro model, GSK343 (1, 10, and 25 μM) significantly decreased OSCC cell viability and cell migration through EZH2 inhibition, modulating NF-κB/IκBα pathway activation and eNOS, VEGF, and TGFβ expression, important markers of angiogenesis. In the in vivo model, GSK343 (5 mg/kg and 10 mg/kg) restored tongue tissue architecture and reduced tumor progression through EZH2 inhibition and Wnt/β-catenin signaling pathway modulation. Moreover, GSK343 reduced the expression of inflammatory mediators; eNOS and TGFβ, markers of angiogenesis; and CD31 and CD34, markers of micro vessel density, respectively. In conclusion, our data demonstrate that GSK343 counteracts oral cancer progression through EZH2/Wnt/β-catenin pathway modulation, suggesting that it could be a promising therapeutic approach for OSCC management.

Neuroinflammatory responses are central to the pathogenesis of neurodegenerative diseases, affecting cells of both neuronal and glial origin that respond to immune-driven inflammatory stimuli. The PI3K/mTOR signaling pathway is essential for the regulation of these neuroinflammatory processes and is therefore a promising target for therapeutic intervention. Here, we investigated the consequences of PI3K/mTOR pathway inhibition on neuroinflammation employing PF-04691502, an agent with combined PI3K and mTOR inhibitory activity. We treated SH-SY5Y, C6, BV-2, and Mo3.13 cell lines with PF-04691502 at concentrations of 0.1, 0.5, and 1 µM to assess the modulation of neuroinflammatory responses. To induce inflammation, cells were stimulated with lipopolysaccharide (LPS, 1 μg/mL) and interferon-gamma (IFN-γ, 100 U/mL). The results from the MTT assays demonstrated that PI3K/mTOR inhibition preserved cell viability at 0.5 and 1 µM across all of the cell lines, indicating its potential to mitigate inflammation-driven cytotoxicity. Subsequent ELISA assays revealed a marked decrease in the NF-κB and pro-inflammatory cytokine levels, confirming the effective suppression of inflammation through PI3K/mTOR inhibition. In addition, the SH-SY5Y cell line was exposed to MPP+ to simulate Parkinson’s disease (PD)-like toxicity; then, cell viability, PD-associated markers, and apoptotic indicators were assessed. Our results indicate that inhibition of the PI3K/mTOR signaling axis may alleviate neurodegenerative processes by modulating both neuroinflammatory responses and apoptotic pathways. These findings highlight the therapeutic promise of targeting PI3K/mTOR in the context of neurodegenerative disorders and support the need for further validation through in vivo and clinical investigations.

Psoriasis is an inflammatory and auto-immune skin-disease characterized by uncontrolled keratinocyte proliferation. Its pathogenesis is not still fully understood; however, an aberrant and excessive inflammatory and immune response can contribute to its progression. Recently, more attention has been given to the anti-inflammatory and immunomodulators effects of melatonin in inflammatory diseases. The aim of this paper was to investigate the effect of melatonin on psoriatic phenotype and also in S. aureus infection-associated psoriasis, with an in vitro model using Skinethic Reconstructed Human Epidermis (RHE). An in vitro model was constructed using the RHE, a three-dimensional-model obtained from human primary-keratinocytes. RHE-cells were exposed to a mix of pro-inflammatory cytokines, to induce a psoriatic phenotype; cells were also infected with S. aureus to aggravate psoriasis disease, and then were treated with melatonin at the concentrations of 1 nM, 10 nM, and 50 nM. Our results demonstrated that melatonin at higher concentrations significantly reduced histological damage, compared to the cytokine and S. aureus groups. Additionally, the treatment with melatonin restored tight-junction expression and reduced pro-inflammatory cytokine levels, such as interleukin-1β and interleukin-12. Our results suggest that melatonin could be considered a promising strategy for psoriasis-like skin inflammation, as well as complications of psoriasis, such as S. aureus infection.