BackgroundDoxorubicin-induced cardiotoxicity (DIC) represents a major limitation in oncology, leading to ventricular dysfunction and long-term morbidity. Lipophilic statins, such as simvastatin, exert pleiotropic effects beyond cholesterol lowering, including antioxidant and anti-inflammatory actions, which may confer cardioprotection.MethodsWe retrospectively analyzed 80 oncology patients treated with anthracycline-based chemotherapy. Clinical, biochemical, and electrocardiographic (ECG) data were collected at baseline and after completion of chemotherapy or during follow-up. Early chemotherapy-related cardiac dysfunction was assessed using ECG markers, including QTa/QTc prolongation and T-wave flattening. Reduced ejection fraction (HFrEF) was defined as left ventricular ejection fraction (LVEF) < 50%. Patients were stratified according to exposure to simvastatin therapy versus no statin treatment. Associations between statin use and cardiac outcomes were evaluated using adjusted regression models; additional propensity score–based weighting analyses were performed to account for potential baseline differences between groups.ResultsSeven patients developed HFrEF. Among patients with preserved LVEF (>60%), 25 developed new ECG abnormalities, whereas 39 maintained normal ECG findings. Statin therapy was strongly associated with protection against ECG alterations: 23 of 25 patients with ECG changes were not receiving statins, while 33 of 39 patients without abnormalities were statin users. Statin-treated patients showed significantly smaller declines in LVEF (ΔLVEF −1.7% vs. −8.0%, p = 0.0017) and reduced prolongation of ventricular repolarization intervals (ΔQT and ΔQTc) compared with non-users. In adjusted analyses, simvastatin exposure remained independently associated with preservation of systolic function and attenuation of QT/QTc prolongation. Statin-treated patients also exhibited lower total and low-density lipoprotein (LDL) cholesterol levels, consistent with expected pharmacologic effects. No clinically relevant differences were observed in atrioventricular or intraventricular conduction parameters. Propensity score–weighted analyses confirmed the robustness of the association between statin therapy and reduced risk of electrocardiographic abnormalities.ConclusionStatin therapy was associated with a lower incidence of early electrocardiographic abnormalities and attenuation of subclinical cardiac dysfunction in patients treated with doxorubicin. These findings suggest that lipophilic statins may mitigate early electrophysiological remodeling and preserve ventricular function during anthracycline therapy, supporting a potential cardioprotective role beyond lipid lowering.

Gastric cancer (GC) remains a major global health challenge, ranking among the most lethal malignancies due to late diagnosis, high tumor heterogeneity, and limited treatment efficacy. The search for safer, nutritionally based adjuncts to conventional therapies is therefore a research priority. Donkey milk (DM), traditionally used as a hypoallergenic substitute for infants, is emerging as a functional food with remarkable bioactivity. Its composition closely resembles human milk, with high levels of bioactive proteins, a favorable polyunsaturated lipid profile, antioxidant vitamins, and immune-supportive minerals. Despite its growing nutraceutical appeal, the anticancer potential of DM in GC has not yet been explored. This study represents the first investigation of DM in human gastric adenocarcinoma (AGS) cells. Using increasing concentrations of whole DM (25-100%), a dose-dependent inhibition of cell viability and migration was observed. Mechanistic insights reveal that DM induces mitochondrial oxidative stress, disrupts cell cycle progression (S/G2 accumulation at 75%, G2 arrest at 100%), and unexpectedly triggers a pro-inflammatory gene signature suggesting stress-driven immunostimulation rather than canonical apoptosis. These findings highlight a non-classical, context-dependent cytotoxic mechanism that distinguishes DM from conventional pro-apoptotic agents. DM may represent a promising nutraceutical candidate for GC management, bridging traditional food resources with modern oncology. By inhibiting hallmark cancer traits while engaging unique immunological pathways, DM offers a sustainable, low-toxicity approach with translational potential. Future studies will focus on the characterization of active components, validation in organoid and animal models, and exploring clinical applications of DM-derived bioactive components in cancer prevention and therapy.

Pancreatic cancer (PC), the fourth cause of cancer-related deaths, is an aggressive disease with an increased worldwide incidence. Pancreatic ductal adenocarcinoma (PDAC), ~90% of pancreatic malignancies, arises from pancreatic ducts. PC has a unique microenvironment hosting a heterogenous combination of cell populations, including immune cells and microbes. Microorganisms appear involved in every step of PC’s natural history, from creating a predisposing environment for in situ carcinogenesis to cell migration and metastasis. Biliary stent placement through endoscopic retrograde cholangiopancreatography (ERCP) can mitigate jaundice in PC patients but may alter the intestinal microbiota and contribute to tumor initiation and progression. Disruption of the antimicrobial barrier of the sphincter of Oddi, due to endoscopic sphincterotomy and stent insertion, promotes duodenal reflux, permitting bacterial colonization and biofilm formation. Although ERCP is the preferred drainage route, studies reported lower complication rate and reduced dysbiosis with percutaneous transhepatic biliary drainage (PTBD). The biliary microbiome in stented patients undergoing pancreaticoduodenectomy is altered, exhibiting higher levels of Enterococci, Klebsiella, and Candida species. The decision to place a biliary stent in PC patients should be carefully considered, given the potential for dysbiosis and its impact on therapeutic resistance. This underscores the need for further research into interventions that could modulate the microbiota, such as PTBD, probiotics or targeted microbial therapies.

Background/Objectives: Clinical application of Doxorubicin (Doxo) is limited by cardiotoxicity, a process strongly associated with an interplay between oxidative stress and inflammatory signaling, particularly Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and Nucleotide oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome engagement. Identifying strategies capable of mitigating these interconnected pathways is of critical importance in cardio-oncology. Simvastatin (SIM) is a promising option since it modulates oxidative stress, inflammation, and cell death through its pleiotropic effects, so this study aimed to evaluate whether SIM attenuates Doxo-induced inflammatory responses. Methods: Human Cardiomyocyte (HCM) cells were pre-treated with SIM (10 µM) for 4 h and then co-exposed to SIM and Doxo (1 µM) for 20 h. Cytofluorimetric analysis was used to evaluate inducible nitric oxide synthase (iNOS), Connexin 43 (Cx43), and Cx43 phosphorylated at Serine 368 (pS368Cx43) levels. Real-time qPCR was performed to evaluate iNOS gene expression, while Nitric oxide (NO) release was evaluated by spectrophotometric analysis. Interleukin (IL)-1β, IL-18, IL-6, tumor necrosis factor alpha (TNF-α) production, and NLRP3 levels were evaluated by means of ELISA assay. Expression levels of inhibitor of nuclear factor kappa B alpha (IκB-α), Caspase-1, and Gasdermin D (GSDMD) were evaluated by Western Blot analysis. Nuclear translocation of NF-κB was evaluated by immunofluorescence assay. Results: In our experimental model, SIM significantly (p < 0.01) reduced Doxo-induced nitrite release, as well as iNOS gene expression (p < 0.05) and protein levels (p < 0.01). SIM also markedly attenuated Doxo-induced NF-κB signaling, pro-inflammatory cytokines production (TNF-α and IL-6, p < 0.01), and inflammosome-related responses (cleaved caspase-1, IL-1β, N-terminal domain of GSDMD), and NLRP3 expression p < 0.05). Additionally, SIM significantly attenuated the overexpression of Cx43 and its phosphorylated form (pS368Cx43), which are responsible for impairing intercellular communication and electrical coupling in cardiomyocytes and contribute to arrhythmias and conduction abnormalities characteristic of acute Doxo-induced cardiotoxicity. Conclusions: Overall, these findings demonstrate that SIM exerts a multifaceted cardioprotective effect against Doxo-induced injury, thereby targeting interconnected inflammatory and pro-arrhythmic pathways implicated in Doxo cardiotoxicity.

BackgroundVaccinium corymbosum berries represent a source of anthocyanins and polyphenols studied and tested for their healthy potential. The present study was aimed at isolating, characterizing, and quantifying the anthocyanin-enriched fraction obtained from blueberry and at assessing its biological and protective effects against head and neck cell lines and under inflammatory-related conditions. V. corymbosum berries extract was subjected to colorimetric analysis, antioxidant evaluation, and HPLC-DAD analysis. This extract was characterized by chlorogenic acid and 12 glycosylated anthocyanins, being the most abundant delphinidin-3-O-galactoside, delphinidin-3-O-arabinoside, malvidin-3-O-galactoside, malvidin-3-O-glucoside, and malvidin-3-O-arabinoside. The blueberry extract (BL) was further used in extensive biological evaluation. Head and neck cell lines, namely CAL27 and A253, were treated at different concentrations in order to evaluate cell migration ability and ErbB receptors and antioxidant enzymes gene expression.ResultsThe gene expression analysis highlighted the capability of BL to reduce ErbB receptors expression in CAL27 cell lines. The same treatments induced an opposite effect in A253 cell line for ErbB2/ErbB3 receptors. Moreover, in A253 cell line, BL increased SOD2 levels and reduced cell migration. The action of BL was also studied in an ex vivo experimental model of colon inflammation and was effective both in reducing the lipopolysaccharide-induced gene expression of different proinflammatory biomarkers involved in colon inflammation, among which tumor necrosis factor alpha, interleukin (IL)-6, and in stimulating the gene expression of the anti-inflammatory cytokine IL-10.ConclusionThe content of specific anthocyanins and chlorogenic acid can be considered responsible of such biological activities providing a new food supplement as coadjuvant of standard therapies.

The growing success of oncologic therapies has led to a significant improvement in patient survival; however, this has been accompanied by an increasing incidence of cardiovascular adverse events, particularly cancer therapy-related cardiac dysfunction (CTRCD). Among these, left ventricular impairment represents a major concern due to its potential to compromise both cardiac and oncologic outcomes. This review provides an in-depth overview of the cardiotoxic adverse events associated with several classes of anticancer agents. Particular focus is given to the molecular mechanisms involved in myocardial injury, such as oxidative stress, mitochondrial dysfunction, calcium dysregulation, endothelial reticulum stress, autophagy, and apoptosis. In parallel, established and emerging cardioprotective strategies, from conventional to newer therapeutic approaches, are explored. The role of advanced imaging modalities, as well as cardiac biomarkers, is discussed in the context of early detection and monitoring of subclinical cardiac injury. Finally, the integration of pharmacogenomics and epigenetics is considered as a promising avenue to personalize risk stratification and preventive therapy. By elucidating the complex interplay between cancer treatments and cardiovascular health, this review underscores the importance of a multidisciplinary, precision medicine approach to optimizing the care of patients undergoing potentially cardiotoxic therapies.

Pancreatic Ductal Adenocarcinoma (PDAC) is currently a major oncological threat given the very low 5-year survival rates of 8-9%. The tumor itself is intertwined with its surrounding tissue in a peculiar tumoral microenvironment (TME) which contributes to resistance against the host immune system and traditional clinical treatments, such as chemotherapy. One of the components of TME is the microbiota, which mainly includes the bacterial species identified in the tumor tissue at various stages. Current literature highlights an active role of the microbiota in tumorigenesis, progression, metastasis, and chemotherapy response in PDAC patients. This review gathered the most recent findings about microbial composition in PDAC patients, along with the effects of intra and extra-tumoral (GI and oral) microbial species on the TME and immune system, their role in tumor progression and immuno-modulation. This paper provides an insight on the potential use of microbes as diagnostic and prognostic markers, and as an additional therapeutic strategy. The study of microbiota offer new ways to slow down carcinogenesis, modulate the immune response, and even serve as an early diagnostic tool in the absence of specific serum markers. In the current review we will offer an inquiry on these potential roles. We sorted out the most recent literature with a comprehensive and critical approach, sourcing papers from PubMed. We exclusively opted for papers that were published in the last 5 years on journals with IF≥4, with a focus on the impact of intra-tumoral microbiome on the natural history of PDAC, from pre-tumoral lesions to metastasis.

Oxidative stress and mitochondrial dysfunction play a key role in the early stage of Doxorubicin (Doxo)-induced cardiotoxicity. Our study investigated the potential cardioprotective role of Simvastatin (Sim), widely known for its antioxidant properties, in an in vitro model of Doxo-induced acute cardiotoxicity. Human Cardiomyocytes (HCMs) were treated with Sim (10 µM, 4 h) and then co-exposed to Doxo (1 µM) and Sim for 20 h. Our data showed that Sim co-treatment significantly (p < 0.05) reduced both cytosolic and mitochondrial Doxo-induced reactive oxygen species overproduction. In Sim co-treated cells, significant reductions in nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression (p < 0.01) and catalase (CAT), heme-oxygenase 1 (HO-1), and superoxide dismutase 2 (SOD2) levels (p < 0.05) compared to Doxo-treated cells were also demonstrated, suggesting a decreased need for compensatory antioxidant defense responses. Moreover, significant reductions in Doxo-induced mitochondrial calcium overload, mitochondrial membrane depolarization (p < 0.005), and apoptosis (p < 0.005) confirmed the protective effects of Sim co-treatment on cardiomyocytes. These data confirm that Sim could be a valuable therapeutic strategy for reducing Doxo-induced HCM damage, preventing the development of dilated cardiomyopathy and long-term heart damage, which are the main limitations of anthracycline use. Finally, real-time PCR analysis revealed that Sim co-treatment significantly reduced (p < 0.001) the Doxo-induced overexpression of MAP4K4, a mitogen-activated protein kinase kinase kinase kinase-4 (MAP4K4) involved in oxidative stress-induced cell death, thus suggesting the involvement of other molecular mechanisms in Sim-mediated cardioprotection.

The aim of this study was to evaluate the antimicrobial efficacy of an air gas soft jet CAP for its potential use in removing oral biofilms, given that plasma-based technologies have emerged as promising methods in periodontology. Two types of biofilms were developed, one by Streptococcus mutans UA 159 bacterial strain and the other by a complex mixture of saliva microorganisms isolated from a patient with periodontitis. This latter biofilm was characterized via Next Generation Sequencing to determine the main bacterial phyla. The CAP source was applied at a distance of 6mm for different time points. A statistically significant reduction of both CFU count and XTT was detected after 60s of CAP treatment, while the treatment for 120s resulted in both biofilms eradication. CLSM analysis supported CAP effectiveness in killing the microorganisms inside the biofilm and in reducing the thickness of the biofilm matrix. Cytotoxicity tests demonstrated the possible use of CAP without important side effects towards human gingival fibroblasts cell line. The current study showed that CAP treatment was able to eradicate preformed biofilms developed by both S. mutans and the complex mixture of saliva microorganisms, representing a potential innovative strategy to counteract oral pathogens responsible for periodontal diseases.

OBJECTIVE:Cold atmospheric plasma (CAP) is a novel approach for cancer treatment. It can be used to treat liquids-plasma-activated media (PAM)-which are then transferred to the target as an exogenous source of reactive oxygen and nitrogen species (RONS). The present study aimed at chemically characterizing different PAM and assessing their in vitro selectivity against head and neck cancer cells (HNC). METHODS:PAM were obtained by exposing 2 and 5 mL of cell culture medium to CAP for 5, 10 and 20 min at a 6 mm working distance. Anions kinetics was evaluated by ion chromatography. Cell proliferation inhibition, apoptosis occurrence, and cell cycle modifications were assessed by MTS and flow cytometry, on human epidermal keratinocyte (HaCaT) and HNC cell lines HSC3, HSC4 and A253. RESULTS:The 2 mL conditions showed a significant reduction in cell proliferation whereas for the 5 mL the effect was milder, but the time-dependence was more evident. HaCaT were unaffected by the 5 mL PAM, indicating a selectivity for cancer cells. CONCLUSIONS:The media chemical composition modified by CAP exposure influenced cell proliferation by modulating cell cycle and inducing apoptosis in cancer cells, without affecting normal cells.

The aim of this study was to evaluate the antimicrobial efficacy of an air gas soft jet CAP for its potential use in removing oral biofilms, given that plasma-based technologies have emerged as promising methods in periodontology. Two types of biofilms were developed, one by Streptococcus mutans UA 159 bacterial strain and the other by a complex mixture of saliva microorganisms isolated from a patient with periodontitis. This latter biofilm was characterized via Next Generation Sequencing to determine the main bacterial phyla. The CAP source was applied at a distance of 6 mm for different time points. A statistically significant reduction of both CFU count and XTT was already detected after 60 s of CAP treatment. CLSM analysis supported CAP effectiveness in killing the microorganisms inside the biofilm and in reducing the thickness of the biofilm matrix. Cytotoxicity tests demonstrated the possible use of CAP without important side effects towards human gingival fibroblasts cell line. The current study showed that CAP treatment was able to significantly reduce preformed biofilms developed by both S. mutans and microorganisms isolated by a saliva sample. Further studies should be conducted on biofilms developed by additional saliva donors to support the potential of this innovative strategy to counteract oral pathogens responsible for periodontal diseases.

During the first year of life, development and balance of newborn gut microbiota are strongly influenced by external factors such as delivery mode, breastfeeding, duration of pregnancy, mother diet and lifestyle, siblings and pets, environment, and antibiotics administration. Gut microbiota colonization starts with facultative anaerobes and continues with the establishment of anaerobic genera of which Bifidobacteria are the gold standard of a healthy gut neonatal microbiota. Scientific literature traditionally describes the fetus as sterile in the womb and identifies the membranes rupture as the beginning of microbial colonization. Vaginal delivery is an important source for the onset of infant colonization which will then continue with the transfer of a new selection of intestinal bacteria with breastfeeding. During cesarean delivery a direct contact of the mouth of newborn with the vaginal and intestinal microbiota is absent, and environmental bacteria play an important role for infants intestinal colonization. Nature has ensured that newborns receive other specific maternal bacteria, through a subsequent method of transfer: breastfeeding. We present a brief and comprehensive state-of-the-art in order to encourage natural childbirth and breastfeeding whenever possible and discuss innovative directions for develop new ad hoc personalized treatments in order to restore physiological microbiota.

Non-cirrhotic portal hypertension (NCPH), also known as idiopathic non-cirrhotic portal hypertension (INCPH) and porto-sinusoidal vascular disorder (PSVD), is a rare disease characterized by intrahepatic portal hypertension (IPH) in the absence of cirrhosis. The precise etiopathogenesis of IPH is an area of ongoing research. NCPH diagnosis is challenging, as there are no specific tests available to confirm the disease, and a high-quality liver biopsy, detailed clinical information, and an expert pathologist are necessary for diagnosis. Currently, the treatment of NCPH relies on the prevention of complications related to portal hypertension, following current guidelines of cirrhotic portal hypertension. No treatment has been studied that aimed to modify the natural history of the disease; however, transjugular intrahepatic porto-systemic shunt (TIPS) placement, shunt and liver transplantation are considerable symptomatic options. In this review, we discuss the heterogeneity of NCPH as well as its etiopathogenesis, clinical presentation and management issues. Starting from the assumption that portal hypertension does not always mean cirrhosis, cooperative studies are probably needed to clarify the issues of etiology and the possible genetic background of this rare disease. This knowledge might lead to better treatment and perhaps better prevention.

Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of death by cancer in the world. What makes this pathological condition particularly lethal is a combination of clinical and molecular heterogeneity, lack of early diagnostic indexes, and underwhelming results from current therapeutic protocols. A major cause of PDAC chemoresistance seems to lie in the ability of cancer cells to spread out and fill the pancreatic parenchyma, exchanging nutrients, substrates, and even genetic material with cells from the surrounding tumor microenvironment (TME). Several components can be found in the TME ultrastructure, including collagen fibers, cancer-associated fibroblasts, macrophages, neutrophils, mast cells, and lymphocytes. Cross-talk between PDAC and TME cells results in the latter being converted into cancer-favoring phenotypes; this behavior could be compared to an influencer guiding followers into supporting his activity. Moreover, TME could be a potential target for some of the newest therapeutic strategies; these include the use of pegvorhyaluronidase-α and CAR-T lymphocytes against HER2, FAP, CEA, MLSN, PSCA, and CD133. Other experimental therapy options are being currently studied, aiming to interfere with the KRAS pathway, DNA-repairing proteins, and apoptosis resistance in PDAC cells. Hopefully these new approaches will grant better clinical outcomes in future patients.

Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer death worldwide. Helicobacter pylori (Hp) infection is an important risk factor for GC. However, the etiology of the tumor is multifactorial, since only 1-3% of infected patients develop cancer. Therefore, attention should be focused on the role of microbiota in gastric tumorigenesis since in some studies an alteration of the microbiota in GC has been shown. Fusobacterium nucleatum (Fn) has been found in biopsies of patients with GC. However, since its role is not clearly established, this study investigated the effects of Fn infection on the human gastric adenocarcinoma cell line AGS. Our results showed that Fn co-localized at level of the plasma membrane demonstrating the ability of Fn to adhere to AGS cells. In addition, increases in incubation times were associated with its intra-cellular localization with loss of the classic curved rod shape. Interestingly, Fn determined a greater capacity of cell migration compared to untreated AGS cells. Moreover, IL-4 expression significantly increased in Fn infected GC cells. Since cancer cell migration is an integral component of the metastatic process, additional studies are needed to better understand the mechanisms underlying the Fn/host interaction.

Gastric cancer is worldwide the fifth and third cancer for incidence and mortality, respectively. Stomach wall is daily exposed to oxidative stress and BER system has a key role in the defense from oxidation-induced DNA damage, whilst ErbB receptors have important roles in the pathogenesis of cancer. We used AGS cells as an aggressive gastric carcinoma cell model, treated with H2O2 alone or combined with ErbB signaling pathway inhibitors, to evaluate the effects of oxidative stress in gastric cancer, focusing on the modulation of ErbB signaling pathways and their eventual cross-talk with BER system. We showed that treatment with H2O2 combined with PI3K/AKT and MEK inhibitors influenced cell morphology and resulted in a reduction of cancer cell viability. Migration ability was reduced after H2O2 treatment alone or combined with MEK inhibitor and after PI3K/AKT inhibitor alone. Western blotting analysis showed that oxidative stress stimulated EGFR pathway favoring the MAPKs activation at the expense of PI3K/AKT pathway. Gene expression analysis by RT-qPCR showed ErbB2 and OGG1 increase under oxidative stress conditions. Therefore, we suggest that in AGS cells a pro-oxidant treatment can reduce gastric cancer cell growth and migration via a different modulation of PI3K and MAPKs pathways. Moreover, the observed ErbB2 and OGG1 induction is a cellular response to protect the cells from H2O2-induced cell death. In conclusion, to tailor specific combinations of therapies and to decide which strategy to use, administration of a chemotherapy that increases intracellular ROS to toxic levels, might not only be dependent on the tumor type, but also on the molecular targeting therapy used.

Thyroid diseases have a complex and multifactorial aetiology. Despite the numerous studies on the signals referable to the malignant transition, the molecular mechanisms concerning the role of oxidative stress remain elusive. Based on its strong oxidative power, H2O2 could be responsible for the high level of oxidative DNA damage observed in cancerous thyroid tissue and hyperactivation of mitogen-activated protein kinase (MAPK) and PI3K/Akt, which mediate ErbB signaling. Increased levels of 8-oxoG DNA adducts have been detected in the early stages of thyroid cancer. These DNA lesions are efficiently recognized and removed by the base excision repair (BER) pathway initiated by 8-oxoG glycosylase1 (OGG1). This study investigated the relationships between the EGFR and OGG1-BER pathways and their mutual regulation following oxidative stress stimulus by H2O2 in human thyrocytes. We clarified the modulation of ErbB receptors and their downstream pathways (PI3K/Akt and MAPK/ERK) under oxidative stress (from H2O2) at the level of gene and protein expression, according to the mechanism defined in a human non-pathological cell system, Nthy-ori 3-1. Later, on the basis of the results obtained by gene expression cluster analysis in normal cells, we assessed the dysregulation of the relationships in a model of papillary thyroid cancer with RET/PTC rearrangement (TPC-1). Our observations demonstrated that a H2O2 stress may induce a physiological cross-regulation between ErbB and OGG1-BER pathways in normal thyroid cells (while this is dysregulated in the TPC-1 cells). Gene expression data also delineated that MUTYH gene could play a physiological role in crosstalk between ErbB and BER pathways and this function is instead lost in cancer cells. Overall, our data on OGG1 protein expression suggest that it was physiologically regulated in response to oxidative modulation of ErbB, and that these might be dysregulated in the signaling pathway involving AKT in the progression of thyroid malignancies with RET/PTC rearrangements.

Over the past decade, we witnessed a promising application of cold atmospheric plasma (CAP) in cancer therapy. The aim of this systematic review was to provide an exhaustive state of the art of CAP employed for the treatment of head and neck cancer (HNC), a tumor whose late diagnosis, local recurrence, distant metastases, and treatment failure are the main causes of patients' death. Specifically, the characteristics and settings of the CAP devices and the in vitro and in vivo treatment protocols were summarized to meet the urgent need for standardization. Its molecular mechanisms of action, as well as the successes and pitfalls of current CAP applications in HNC, were discussed. Finally, the interesting emerging preclinical hypotheses that warrant further clinical investigation have risen. A total of 24 studies were included. Most studies used a plasma jet device (54.2%). Argon resulted as the mostly employed working gas (33.32%). Direct and indirect plasma application was reported in 87.5% and 20.8% of studies, respectively. In vitro investigations were 79.17%, most of them concerned with direct treatment (78.94%). Only eight (33.32%) in vivo studies were found; three were conducted in mice, and five on human beings. CAP showed pro-apoptotic effects more efficiently in tumor cells than in normal cells by altering redox balance in a way that oxidative distress leads to cell death. In preclinical studies, it exhibited efficacy and tolerability. Results from this systematic review pointed out the current limitations of translational application of CAP in the urge of standardization of the current protocols while highlighting promising effects as supporting treatment in HNC.

Following a similar approach on carvacrol-based derivatives, we investigated the synthesis and the microbiological screening against eight strains of H. pylori, and the cytotoxic activity against human gastric adenocarcinoma (AGS) cells of a new series of ether compounds based on the structure of thymol. Structural analysis comprehended elemental analysis and 1H/13C/19F NMR spectra. The analysis of structure–activity relationships within this molecular library of 38 structurally-related compounds reported that some chemical modifications of the OH group of thymol led to broad-spectrum growth inhibition on all isolates. Preferred substitutions were benzyl groups compared to alkyl chains, and the specific presence of functional groups at para position of the benzyl moiety such as 4-CN and 4-Ph endowed the most anti-H. pylori activity toward all the strains with minimum inhibitory concentration (MIC) values up to 4 µg/mL. Poly-substitution on the benzyl ring was not essential. Moreover, several compounds characterized by the lowest minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) values against H. pylori were also tested in order to verify a cytotoxic effect against AGS cells with respect to 5-fluorouracil and carvacrol. Three derivatives can be considered as new lead compounds alternative to current therapy to manage H. pylori infection, preventing the occurrence of severe gastric diseases. The present work confirms the possibility to use natural compounds as templates for the medicinal semi-synthesis.

Worldwide, gastric cancer (GC) represents the fifth cancer for incidence, and the third as cause of death in developed countries. Indeed, it resulted in more than 780,000 deaths in 2018. Helicobacter pylori appears to be responsible for the majority of these cancers. On the basis of recent studies, and either alone or combined with additional etiological factors, H. pylori is considered a “type I carcinogen.” Over recent decades, new insights have been obtained into the strategies that have been adopted by H. pylori to survive the acidic conditions of the gastric environment, and to result in persistent infection, and dysregulation of host functions. The multistep processes involved in the development of GC are initiated by transition of the mucosa into chronic non-atrophic gastritis, which is primarily triggered by infection with H. pylori. This gastritis then progresses into atrophic gastritis and intestinal metaplasia, and then to dysplasia, and following Correa’s cascade, to adenocarcinoma. The use of antibiotics for eradication of H. pylori can reduce the incidence of precancerous lesions only in the early stages of gastric carcinogenesis. Here, we first survey the etiology and risk factors of GC, and then we analyze the mechanisms underlying tumorigenesis induced by H. pylori, focusing attention on virulence factor CagA, inflammation, oxidative stress, and ErbB2 receptor tyrosine kinase. Moreover, we investigate the relationships between H. pylori eradication therapy and other diseases, considering not only cardia (upper stomach) cancers and Barrett’s esophagus, but also asthma and allergies, through discussion of the “hygiene hypothesis. ” This hypothesis suggests that improved hygiene and antibiotic use in early life reduces microbial exposure, such that the immune response does not become primed, and individuals are not protected against atopic disorders, asthma, and autoimmune diseases. Finally, we overview recent advances to uncover the complex interplay between H. pylori and the gut microbiota during gastric carcinogenesis, as characterized by reduced bacterial diversity and increased microbial dysbiosis. Indeed, it is of particular importance to identify the bacterial taxa of the stomach that might predict the outcome of gastric disease through the stages of Correa’s cascade, to improve prevention and therapy of gastric carcinoma.