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Unraveling vulnerabilities in chronic lymphocytic leukemia (CLL) represents a key approach to understand molecular basis for its indolence and a path toward developing tailored therapeutic approaches. In this study, we found that CLL cells are particularly sensitive to the inhibitory action of abundant serum protein, apolipoprotein E (ApoE). Physiological concentrations of ApoE affect CLL cell viability and inhibit CD40-driven proliferation. Transcriptomics of ApoE-treated CLL cells revealed a signature of redox and metal disbalance which prompted us to explore the underlying mechanism of cell death. We discover, on one hand, that ApoE treatment of CLL cells induces lipid peroxidation and ferroptosis. On the other hand, we find that ApoE is a copper-binding protein and that intracellular copper regulates ApoE toxicity. ApoE regulation tends to be lost in aggressive CLL. CLL cells from patients with high leukocyte counts are less sensitive to ApoE inhibition, while resistance to ApoE is possible in transformed CLL cells from patients with Richter syndrome (RS). Nevertheless, both aggressive CLL and RS cells maintain sensitivity to drug-induced ferroptosis. Our findings suggest a natural suppression axis that mediates ferroptotic disruption of CLL cell proliferation, building up the rationale for choosing ferroptosis as a therapeutic target in CLL and RS., (© 2024. The Author(s).)

Fermented foods have regained popularity in Western diets for their health-promoting potential, mainly related to the role of lactic acid bacteria (LAB) during the fermentation process. Nowadays, there is an increasing demand for vegetable-based fermented foods, representing an environmentally sustainable options to overcome the limitations of lactose intolerance, vegetarian, or cholesterol-restricted diets. Among them, table olives and their co-products (i.e., olive pomace) represent important plant-origin matrices, whose exploitation is still limited. Olives are an important source of fiber and bioactive molecules such as phenolic compounds with recognized health-promoting effects. Based on that, this minireview offer a brief overview about the potential beneficial role of fermented table olives/olive pomace, with a particular focus on the role of LAB to obtain healthy and/or probiotic-enriched fermented foods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Montagano, Dell’Orco, Prete and Corsetti.)

Environmental pollutants used as plasticizers in food packaging and in thousands of everyday products have become harmful for their impact on human health. Among them, phthalates, recognized as emerging endocrine disruptors (EDs) can induce toxic effects leading to different health disorders. Only few studies evaluated the effects of di-n-hexyl phthalate (DnHP) in in vivo models and no studies have been conducted to investigate the effect of DnHP on the endocannabinoid system (ECS), one of the majors signaling pathways involved in the microbiota-gut-brain axis. Due to the current relevance of probiotic bacteria as beneficial dietary interventions, the present study was aimed at evaluating the potential neuroprotective impact of daily administration of Lactiplantibacillus (Lpb.) plantarum IMC513 on zebrafish adults exposed to DnHP, with a focus on ECS modulation. Gene expression analysis revealed a promising protective role of probiotic through the restoration of ECS genes expression to the control level, in the brain of zebrafish daily exposed to DnHP. In addition, the levels of main endocannabinoids were also modulated. These findings confirm the potential ability of probiotics to interact at central level by modulating the ECS, suggesting the use of probiotics as innovative dietary strategy to counteract alterations by EDs exposure., (© 2024. The Author(s).)

Competing Interests: The authors declare no conflict of interest.

Glucose catabolism, one of the essential pathways sustaining cellular bioenergetics, has been widely studied in the context of tumors. Nevertheless, the function of various branches of glucose metabolism that stem from 'classical' glycolysis have only been partially explored. This review focuses on discussing general mechanisms and pathological implications of glycolysis and its branching pathways in the biology of B cell malignancies. We summarize here what is known regarding pentose phosphate, hexosamine, serine biosynthesis, and glycogen synthesis pathways in this group of tumors. Despite most findings have been based on malignant B cells themselves, we also discuss the role of glucose metabolism in the tumor microenvironment, with a focus on T cells. Understanding the contribution of glycolysis branching pathways and how they are hijacked in B cell malignancies will help to dissect the role they have in sustaining the dissemination and proliferation of tumor B cells and regulating immune responses within these tumors. Ultimately, this should lead to deciphering associated vulnerabilities and improve current therapeutic schedules., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Exopolysaccharides (EPSs) producing lactic acid bacteria have been claimed to confer various health benefits to the host, including the ability to face oxidative and inflammatory-related stress. This study investigated the ability of food-borne Lactiplantibacillus ( Lpb. ) plantarum to improve the antioxidant activity of fermented milks by producing EPSs. Two Lpb. plantarum strains, selected as lower and higher EPSs producers, have been applied in lab-scale fermented milk production, in combination with conventional starters. Antioxidant activity was investigated in vitro using DPPH (1,1-diphenyl-2-picrylhydrazyl), ABTS (2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and FRAP (ferric reducing antioxidant power) assays while the ability to modulate reactive oxygen species (ROS) level was evaluated in an intestinal healthy model, subjected to both oxidative and inflammatory stress. Furthermore, to verify whether digestion affects functionality, fermented milks were evaluated before and after in vitro-simulated INFOGEST digestion. The results showed an improved antioxidant activity of fermented milk enriched with Lpb. plantarum LT100, the highest EPSs producer. Furthermore, the data showed a different ROS modulation with a protective anti-inflammatory effect of samples enriched with Lpb. plantarum strains. Our data suggest the use of selected EPS-producing strains of Lpb. plantarum as a natural strategy to enrich the functionality of fermented milks in terms of ROS modulation and inflammatory-related stress.

Background: The current manuscript's aim was to determine the human papillomavirus (HPV) genotype-specific prevalence and distribution among individuals, males, and females, of different ages in the region of Apulia, Italy, highlighting the possible variables involved in the carcinogenicity mechanism. In addition, we proposed two hypothetical models of HPV's molecular dynamics, intending to clarify the impact of prevention and therapeutic strategies, explicitly modeled by recent survey data., Methods: We presented clinical data from 9647 participants tested for either high-risk (HR) or low-risk (LR) HPV at the affiliated Bari Policlinic University Hospital of Bari from 2011 to 2022. HPV DNA detection was performed using nested-polymerase chain reaction (PCR) and multiplex real-time PCR assay. Statistical analysis showed significant associations for all genders and ages and both HR- and LR-HPV types. A major number of significant pairwise associations were detected for the higher-risk types and females and lower-risk types and males., Results: The overall prevalence of HPV was 50.5% (n-4.869) vs. 49.5% (n-4.778) of the study population, of which 74.4% (n-3621) were found to be HPV high-risk (HR-HPV) genotypes and 57.7% (n-2.807) low-risk HPV (LR-HPV) genotypes, of which males were 58% and females 49%; the three most prevalent HR-HPV genotypes were HPV 53 (n707-15%), 16 (n704-14%), and 31 (n589-12%), and for LR-HPV, they were 42 (19%), 6 (16%), and 54 (13%); 56% of patients screened for HPV were ≤ 30 years old, 53% were between 31 and 40 years old, 46% were 41-50 and 51-60 years old, and finally, 44% of subjects were >60 years old., Conclusions: Our study provided comprehensive epidemiological data on HPV prevalence and genotype distribution among 9647 participants, which could serve as a significant reference for clinical practice, and it implied the necessity for more effective screening methods for HPV carcinogenesis covering the use of more specific molecular investigations. Although this is a predominantly descriptive and epidemiological study, the data obtained offer not only a fairly unique trend compared to other studies of different realities and latitudes but also lead us to focus on the HPV infection within two groups of young people and adults and hypothesize the possible involvement of dysbiosis, stem cells, and the retrotransposition mechanism.

This study investigated the main microbial groups characterizing the interior surface of oak barrels from different years (1890, 1895, 1920, 1975, 2008) used in the production of vino cotto. The yeasts were characterized for the following properties: γ-aminobutyric acid (GABA) production, antioxidant activity, air-liquid interfacial biofilm formation, and anthocyanin adsorption capacity. Community-level physiological profile analysis revealed that the microbial communities inside the barrels used the tested carbon sources in different manners. The following yeast species were identified: Millerozyma farinosa , Zygosaccharomyces bisporus , Wickerhamiella versatilis , Zygosaccharomyces bailii , Starmerella lactis-condensi , and Zygosaccharomyces rouxii . All the strains were able to produce GABA, and S. lactis-condensi , Z. bisporus and Z. rouxii were the highest producers (more than 600 mg/L). The Z. rouxii and Z. bailii strains showed the highest antioxidant activity. Only seven strains out of ten M. farinosa formed air-liquid interfacial biofilm. None of the M. farinosa strains adsorbed anthocyanins on their cell wall. The other strains adsorbed anthocyanins in a strain-dependent way, and the highest adsorption was observed for the W. versatilis strains. The yeasts isolated in this study could be used to increase the functional properties and the quality of fermented foods and beverages.

Coronavirus disease-2019 (COVID-19) is a respiratory disease in which Spike protein from SARS-CoV-2 plays a key role in transferring virus genomic code into target cells. Spike protein, which is found on the surface of the SARS-CoV-2 virus, latches onto angiotensin-converting enzyme 2 receptors (ACE2r) on target cells. The RNA genome of coronaviruses, with an average length of 29 kb, is the longest among all RNA viruses and comprises six to ten open reading frames (ORFs) responsible for encoding replicase and structural proteins for the virus. Each component of the viral genome is inserted into a helical nucleocapsid surrounded by a lipid bilayer. The Spike protein is responsible for damage to several organs and tissues, even leading to severe impairments and long-term disabilities. Spike protein could also be the cause of the long-term post-infectious conditions known as Long COVID-19, characterized by a group of unresponsive idiopathic severe neuro- and cardiovascular disorders, including strokes, cardiopathies, neuralgias, fibromyalgia, and Guillaume-Barret's like-disease. In this paper, we suggest a pervasive mechanism whereby the Spike proteins either from SARS-CoV-2 mRNA or mRNA vaccines, tend to enter the mature cells, and progenitor, multipotent, and pluripotent stem cells (SCs), altering the genome integrity. This will eventually lead to the production of newly affected clones and mature cells. The hypothesis presented in this paper proposes that the mRNA integration into DNA occurs through several components of the evolutionarily genetic mechanism such as retrotransposons and retrotransposition, LINE-1 or L1 (long interspersed element-1), and ORF-1 and 2 responsible for the generation of retrogenes. Once the integration phase is concluded, somatic cells, progenitor cells, and SCs employ different silencing mechanisms. DNA methylation, followed by histone modification, begins to generate unlimited lines of affected cells and clones that form affected tissues characterized by abnormal patterns that become targets of systemic immune cells, generating uncontrolled inflammatory conditions, as observed in both Long COVID-19 syndrome and the mRNA vaccine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Nowadays, Western diets and lifestyle lead to an increasing occurrence of chronic gut inflammation that represents an emerging health concern with still a lack of successful therapies. Fermented foods, and their associated lactic acid bacteria, have recently regained popularity for their probiotic potential including the maintenance of gut homeostasis by modulating the immune and inflammatory response. Our study aims to investigate the crosstalk between the food-borne strain Lactiplantibacillus plantarum C9O4 and intestinal epithelial cells in an in vitro inflammation model. Cytokines profile shows the ability of C9O4 to significantly reduce levels of IL-2, IL-5, IL-6, and IFN-γ. Proteomic functional analysis reveals an immunoregulatory role of C9O4, able to revert the detrimental effects of IFN-γ through the JAK/STAT pathway in inflamed intestinal cells. These results suggest a promising therapeutic role of fermented food-associated microbes for the management of gastrointestinal inflammatory diseases. Data are available via ProteomeXchange with identifier PXD042175., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

During the Sars-Cov-2 pandemic, Stenotrophomonas maltophilia (S.maltophilia) secondary pulmonary infections have increased, especially in critically ill patients, highlighting the need for new therapeutic options. Trimethoprim-sulfamethoxazole (SXT) is the treatment of choice but the increase of resistant strains or adverse drug reactions limited its clinical use. Recently ceftazidime/avibactam (CZA) has been approved for the treatment of multi drug resistant (MDR) Gram-negative bacteria infections, including hospital acquired pneumonia. The aim of this study was to evaluate the in vitro activity of ceftazidime/avibactam (CZA) alone and in combination with aztreonam (ATM) against S. maltophilia clinical isolates by E-test method. Susceptibility of SXT and levofloxacin (LEV) was also investigated. Our results showed 22% of resistance to CZA, 2% to SXT and 26% to LEV. CZA in combination with ATM demonstrated synergistic activity against 86% of the strains, including all those resistant to CZA. The combination of CZA with ATM provides a new therapeutic option for the treatment of severe respiratory infections in critically ill patients.

Introduction: Edible insects have been recognized as a more sustainable source of nutrients and bio-active compounds than animal-based products, in line with classical vegetable sources such as legumes. In this study, we assessed the antioxidant properties of four edible insects (silkworms, grasshoppers, mealworms and giant worms) and four legume seeds (lentils, chickpeas, Roveja peas and grass peas)., Methods: After the aqueous extraction or in vitro simulated digestion process, selected products were assessed for: (i) in vitro antioxidant capacity through Ferric Reducing Antioxidant Power (FRAP) assay; (ii) the ability to reduce free radicals production induced by a pro-oxidant agent in cells of human colonic mucosa., Results: All the aqueous extracts and digesta of edible insects displayed significantly higher in vitro antioxidant activity than legumes. Moreover, edible insects at all tested concentrations were able to exert an antioxidant effect in the cellular model, while legumes were effective mainly at high concentrations., Discussion: Despite human trials are need to confirm and define these results in a physiological situation, here we suggest a role for edible insects in oxidative stress prevention. Since oxidative stress is strongly correlated with several intestinal pathologies, the results obtained could be interesting for the prevention and relief of the negative symptoms, offering new advantages to their already known ecological and nutritional properties., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 D’Antonio, Battista, Di Mattia, Sacchetti, Ramal-Sanchez, Prete, Angelino and Serafini.)

Background and Aim: Since December 2019, the Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2), has spread from China, becoming a pandemic. Bacterial and fungal co-infections may lead to increase in COVID-19 severity with a decrease in patients survive. The aim of this work was to evaluate bacterial and fungal co-infections in COVID-19 patients admitted to ICU in comparison with patients recovered in ICU in pre-COVID-19 era in order to understand whether the pandemic had changed the incidence of overinfections in patients admitted to ICU. In fact, the epidemiological data should guide the choice of empirical therapy., Methods: During pandemic, AOUC Policlinico of Bari organized dedicated ICUs for patient with SARS-CoV-2. Blood cultures, urine, and tracheobronchial aspirate were included in the analysis., Results: Specimens of 1905 patients were analysed in this work. Comparing clinical isolates prevalence by material and COVID-19 vs. non-COVID-19 patients statistically significant differences were detected for A. baumannii complex, Aspergillus fumigatus, Escherichia coli, Haemophilus influenzae and Serratia marcescens isolated from tracheobronchial aspirates; C. albicans from urine samples, A. baumannii complex, Enterococcus faecalis and Enterococcus faecium isolated from blood culture., Conclusions: Although the organisms isolated in COVID-19 patients are consistent with those frequently associated with healthcare associated infection, our data suggest a particular prevalence in COVID-19 patients of A. baumannii, Stenotrophomonas maltophilia and Aspergillus spp. in the respiratory tract, C. albicans in urine and  A. baumannii, E. faecalis and E. faecium in blood cultures.

Shortly after its emergence, Omicron and its sub-variants have quickly replaced the Delta variant during the current COVID-19 outbreaks in Vietnam and around the world. To enable the rapid and timely detection of existing and future variants for epidemiological surveillance and diagnostic applications, a robust, economical real-time PCR method that can specifically and sensitively detect and identify multiple different circulating variants is needed. The principle of target- failure (TF) real-time PCR is simple. If a target contains a deletion mutation, then there is a mismatch with the primer or probe, and the real-time PCR will fail to amplify the target. In this study, we designed and evaluated a novel multiplex RT real-time PCR (MPL RT-rPCR) based on the principle of target failure to detect and identify different variants of SARS-CoV-2 directly from the nasopharyngeal swabs collected from COVID-19 suspected cases. The primers and probes were designed based on the specific deletion mutations of current circulating variants. To evaluate the results from the MPL RT-rPCR, this study also designed nine pairs of primers for amplifying and sequencing of nine fragments from the S gene containing mutations of known variants. We demonstrated that (i) our MPL RT-rPCR was able to accurately detect multiple variants that existed in a single sample; (ii) the limit of detection of the MPL RT-rPCR in the detection of the variants ranged from 1 to 10 copies for Omicron BA.2 and BA.5, and from 10 to 100 copies for Delta, Omicron BA.1, recombination of BA.1 and BA.2, and BA.4; (iii) between January and September 2022, Omicron BA.1 emerged and co-existed with the Delta variant during the early period, both of which were rapidly replaced by Omicron BA.2, and this was followed by Omicron BA.5 as the dominant variant toward the later period. Our results showed that SARS-CoV-2 variants rapidly evolved within a short period of time, proving the importance of a robust, economical, and easy-to-access method not just for epidemiological surveillance but also for diagnoses around the world where SARS-CoV-2 variants remain the WHO's highest health concern. Our highly sensitive and specific MPL RT-rPCR is considered suitable for further implementation in many laboratories, especially in developing countries.

Pea proteins are being increasingly used for the formulation of plant-based products, but their globular structure and the presence of aggregates can affect their technological properties. In this study, the effect of high pressure homogenization (HPH) at different intensities (60 and 100 MPa) was investigated as a pre-treatment to modulate the techno-functional properties of a pea protein isolate (IP) extracted through an alkaline extraction/isoelectric precipitation process. SDS-PAGE, circular dichroism, thermal properties, total free sulfhydryl groups, antioxidant capacity and reducing properties were evaluated along with technological indices as solubility, WHC and OHC, interfacial tension and emulsifying capacity. HPH treatments were able to unfold and modify proteins structure, leading also to a change of the relative abundance of pea protein globulins (SDS-PAGE) and of the vicilin to legumin ratio. Solubility, WHC and OHC were improved, while interfacial tension and emulsifying capacity were weakly affected. However, an enhanced physical stability over time of the emulsions prepared with the 60 MPa-treated protein was found, likely as an effect of the decreased ratio between vicilin and legumin after treatment. Results of this study will contribute to deepen the effect of the HPH technology used as pre-treatment, adding useful results and expanding knowledge about the structure and techno-functional properties of native and modified pea proteins., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Chlamydia trachomatis and human papillomavirus (HPV) are the most common pathogens found in sexually transmitted infections (STIs), and both are known to increase the risk of cervical cancer (CC) and infertility. HPV is extremely common worldwide, and scientists use it to distinguish between low-risk and high-risk genotypes. In addition, HPV transmission can occur via simple contact in the genital area. From 50 to 80% of sexually active individuals become infected with both C. trachomatis and HPV viruses during their lifetime, and up to 50% become infected with an HPV oncogenic genotype. The natural history of this coinfection is strongly conditioned by the balance between the host microbiome and immune condition and the infecting agent. Though the infection often regresses, it tends to persist throughout adult life asymptomatically and silently. The partnership between HPV and C. trachomatis is basically due to their similarities: common transmission routes, reciprocal advantages, and the same risk factors. C. trachomatis is a Gram-negative bacteria, similar to HPV, and an intracellular bacterium, which shows a unique biphasic development that helps the latter continue its steady progression into the host throughout the entire life. Indeed, depending on the individual's immune condition, the C. trachomatis infection tends to migrate toward the upper genital tract and spread to the uterus, and the fallopian tubes open up a pathway to HPV invasion. In addition, most HPV and C. trachomatis infections related to the female genital tract are facilitated by the decay of the first line of defense in the vaginal environment, which is constituted by a healthy vaginal microbiome that is characterized by a net equilibrium of all its components. Thus, the aim of this paper was to highlight the complexity and fragility of the vaginal microenvironment and accentuate the fundamental role of all elements and systems involved, including the Lactobacillus strains ( Lactobacillus gasseri, Lactobacillus jensenii, Lactobacillus crispatus ) and the immune-endocrine system, in preserving it from oncogenic mutation. Therefore, age, diet, and genetic predisposition together with an unspecific, persistent low-grade inflammatory state were found to be implicated in a high frequency and severity grade of disease, potentially resulting in pre-cancerous and cancerous cervical lesions.

Life is based on a highly specific combination of atoms, metabolism, and genetics which eventually reflects the chemistry of the Universe which is composed of hydrogen, oxygen, nitrogen, sulfur, phosphorus, and carbon. The interaction of atomic, metabolic, and genetic cycles results in the organization and de-organization of chemical information of that which we consider as living entities, including cancer cells. In order to approach the problem of the origin of cancer it is therefore reasonable to start from the assumption that the sub-molecular level, the atomic structure, should be the considered starting point on which metabolism, genetics, and external insults eventually emanate. Second, it is crucial to characterize which of the entities and parts composing human cells may live a separate life; certainly, this theoretical standpoint would consider mitochondria, an organelle of "bacteria" origin embedded in conditions favorable for the onset of both. This organelle has not only been tolerated by immunity but has also been placed as a central regulator of cell defense. Virus, bacteria, and mitochondria are also similar in the light of genetic and metabolic elements; they share not only equivalent DNA and RNA features but also many basic biological activities. Thus, it is important to finalize that once the cellular integrity has been constantly broken down, the mitochondria like any other virus or bacteria return to their original autonomy to simply survive. The Warburg's law that states the ability of cancers to ferment glucose in the presence of oxygen, indicates mitochondria respiration abnormalities may be the underlying cause of this transformation towards super cancer cells. Though genetic events play a key part in altering biochemical metabolism, inducing aerobic glycolysis, this is not enough to impair mitochondrial function since mitochondrial biogenesis and quality control are constantly upregulated in cancers. While some cancers have mutations in the nuclear-encoded mitochondrial tricarboxylic acid (TCA) cycle, enzymes that produce oncogenic metabolites, there is also a bio-physic pathway for pathogenic mitochondrial genome mutations. The atomic level of all biological activities can be considered the very beginning, marked by the electron abnormal behavior that consequently affects DNA of both cells and mitochondria. Whilst the cell's nucleus DNA after a certain number of errors and defection tends to gradually switch off, the mitochondria DNA starts adopting several escape strategies, switching-on a few important genes that belong back at their original roots as independent beings. The ability to adopt this survival trick, by becoming completely immune to current life-threatening events, is probably the beginning of a differentiation process towards a "super-power cell", the cancer cells that remind many pathogens, including virus, bacteria, and fungi. Thus, here, we present a hypothesis regarding those changes that first begin at the mitochondria atomic level to steadily involve molecular, tissue and organ levels in response to the virus or bacteria constant insults that drive a mitochondria itself to become an "immortal cancer cell". Improved insights into this interplay between these pathogens and mitochondria progression may disclose newly epistemological paradigms as well as innovative procedures in targeting cancer cell progressive invasion., Competing Interests: Authors declare no conflict of interest.

The diffusion of antibiotic-resistant, Gram-negative, opportunistic pathogens, an increasingly important global public health issue, causes a significant socioeconomic burden. Acinetobacter baumannii isolates, despite causing a lower number of infections than Enterobacterales, often show multidrug-resistant phenotypes. Carbapenem resistance is also rather common, prompting the WHO to include carbapenem-resistant A. baumannii as a "critical priority" for the discovery and development of new antibacterial agents. In a previous work, we identified several series of compounds showing either direct-acting or synergistic activity against relevant Gram-negative species, including A. baumannii. Among these, two pyrazole compounds, despite being devoid of any direct-acting activity, showed remarkable synergistic activity in the presence of a subinhibitory concentration of colistin on K. pneumoniae and A. baumannii and served as a starting point for the synthesis of new analogues. In this work, a new series of 47 pyrazole compounds was synthesized. Some compounds showed significant direct-acting antibacterial activity on Gram-positive organisms. Furthermore, an evaluation of their activity as potential antibiotic adjuvants allowed for the identification of two highly active compounds on MDR Acinetobacter baumannii , including colistin-resistant isolates. This work confirms the interest in pyrazole amides as a starting point for the optimization of synergistic antibacterial compounds active on antibiotic-resistant, Gram-negative pathogens.

In order to develop properly, the brain requires the intricate interconnection of genetic factors and pre-and postnatal environmental events. The gut-brain axis has recently raised considerable interest for its involvement in regulating the development and functioning of the brain. Consequently, alterations in the gut microbiota composition, due to antibiotic administration, could favor the onset of neurodevelopmental disorders. Literature data suggest that the modulation of gut microbiota is often altered in individuals affected by neurodevelopmental disorders. It has been shown in animal studies that metabolites released by an imbalanced gut-brain axis, leads to alterations in brain function and deficits in social behavior. Here, we report the potential effects of antibiotic administration, before and after birth, in relation to the risk of developing neurodevelopmental disorders. We also review the potential role of probiotics in treating gastrointestinal disorders associated with gut dysbiosis after antibiotic administration, and their possible effect in ameliorating neurodevelopmental disorder symptoms.

Objectives: After a chronic intestinal injury, several intestinal cells switch their phenotype to activated myofibroblasts, which in turn release an abnormal amount of extracellular matrix proteins, leading to the onset of the fibrotic process. To date, no resolutive pharmacological treatments are available, and the identification of new therapeutic approaches represents a crucial goal to achieve. The onset, maintenance, and progression of inflammatory bowel disease are related to abnormal intestinal immune responses to environmental factors, including diet and intestinal microflora components. This study aimed to evaluate the potential antiinflammatory and antifibrotic effect of a biologically debittered olive cream and its probiotic oral administration in an experimental model of dextran sodium sulfate (DSS)-induced chronic colitis., Methods: Chronic colitis was induced in mice by three cycles of oral administration of 2.5% DSS (5 d of DSS followed by 7 d of tap water). Mice were randomly divided into five groups: 10 control mice fed with standard diet (SD), 20 mice receiving SD and DSS (SD+DSS), 20 mice receiving an enriched diet (ED) with olive cream and DSS (ED+DSS), 20 mice receiving SD plus probiotics (PB; Lactiplantibacillus plantarum IMC513) and DSS (SD+PB+DSS), and 20 mice receiving ED plus PB and DSS (ED+ PB+DSS). Clinical features and large bowel macroscopic, histologic, and immunohistochemical findings were evaluated., Results: The simultaneous administration of ED and PB induced a significant reduction in macroscopic and microscopic colitis scores compared with the other DSS-treated groups. In addition, ED and PB led to a significant decrease in the expression of inflammatory cytokines and profibrotic molecules., Conclusions: The concomitant oral administration of a diet enriched with biologically debittered olive cream and a specific probiotic strain (Lactiplantibacillus plantarum IMC513) can exert synergistic antiinflammatory and antifibrotic action in DSS-induced chronic colitis. Further studies are needed to define the cellular and molecular mechanisms modulated by olive cream compounds and by Lactiplantibacillus plantarum IMC513., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

This article aims to investigate about the social stigma and the prejudice of society towards the patients with leprosy, but also to understand how this infectious disease has largely influenced human lifestyle and evolution analyzing the evolution of its treatments from past empirical treatments to actual multidrug therapy (MDT). References on leprosy were extensively searched in literature using PubMed, Web of Science, Medline, Springer link and Elsevier's (EMBASE.com) databases, but also in medical, religious and archaeological books. Leprosy's spread all around the world following human paths of migration from the African Continent to the Asian one and to Europe, instead its appearance in the New Continent is more recent. Wars, unhygienic conditions, social and health inequality created conditions for its spread since prehistorical times, and existing health disparities contributed to unequal morbidity and mortality, before its gradual decline after the Middle Ages due to the raise of other worse pandemics. Starting from Renaissance, a deeper knowledge on its pathophysiological mechanisms brought an increasingly advanced combined surgical and pharmacological treatment, but still in modern times many efforts have been made to erase its social stigma, changing its name in "Hansen's disease" included., Competing Interests: Conflict of interest None., (Copyright © 2016 - 2021 InfezMed.)

Background: Human Papillomavirus (HPV) role in oral potentially malignant lesions remains unclear. Aims of this study were to evaluate the prevalence of HPV infection in a cohort of patients affected by oral lichen planus, to analyze the genotypes involved, and to compare the performance of two specimen collection methods: brushing and biopsy., Methods: Consecutive patients with oral lichen planus were enrolled. Each patient's clinical and anamnestic data were recorded before he/she underwent brushing and biopsy procedures. The collected samples were analyzed using RT-PCR. Prevalence of HPV infection was evaluated considering cytobrush and biopsy outcomes alone and combined. Correlation between HPV presence and sex, age, smoke, alcohol, kind of lichen planus, Hepatitis C virus, and involved mucosae was analyzed using chi-square test (significance at P < .05). Cohen's k coefficient was employed to compare brushing and biopsy., Results: Fifty-two patients affected by oral lichen planus were enrolled. Total HPV prevalence was 17%, when considering only the biopsy and the cytobrush the prevalence was 15% and 6%, respectively. None of the considered variables showed significant correlation with HPV (P > .05). The concordance between the two methods was "fair" (k = .305)., Conclusions: The biopsy appears more reliable than cytobrush to detect HPV in course of oral lichen planus. No statistical correlation emerged with the analyzed variables. The most frequently detected genotypes were HPV 6 and 11, while only two cases presented with HPV 16 and 53, known as human oncogenic., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The reciprocal parent of origin-specific expression of H19 and IGF2 is controlled by the H19/IGF2:IG-DMR (IC1), whose maternal allele is unmethylated and acts as a CTCF-dependent insulator. In humans, internal IC1 deletions are associated with Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS), depending on their parental origin. These genetic mutations result in aberrant DNA methylation, deregulation of IGF2/H19 and disease with incomplete penetrance. However, the mechanism linking the microdeletions to altered molecular and clinical phenotypes remains unclear. To address this issue, we have previously generated and characterized two knock-in mouse lines with the human wild-type (hIC1wt) or mutant (hIC1∆2.2) IC1 allele replacing the endogenous mouse IC1 (mIC1). Here, we report an additional knock-in line carrying a mutant hIC1 allele with an internal 1.8 kb deletion (hIC1∆1.8). The phenotype of these mice is different from that of the hIC1∆2.2-carrying mice, partially resembling hIC1wt animals. Indeed, proper H19 and Igf2 imprinting and normal growth phenotype were evident in the mice with maternal transmission of hIC1Δ1.8, while low DNA methylation and non-viable phenotype characterize its paternal transmission. In contrast to hIC1wt, E15.5 embryos that paternally inherit hIC1Δ1.8 displayed variegated hIC1 methylation. In addition, increased Igf2 expression, correlating with increased body weight, was found in one third of these mice. Chromatin immunoprecipitation experiments in mouse embryonic stem cells carrying the three different hIC1 alleles demonstrate that the number of CTCF target sites influences its binding to hIC1, indicating that in the mouse, CTCF binding is key to determining hIC1 methylation and Igf2 expression., (© The Author(s) 2021. Published by Oxford University Press.)

Lactic acid bacteria (LAB) used in the food industry, mainly for the production of dairy products, are able to synthetize exopolysaccharides (EPS). EPS play a central role in the assessment of rheological and sensory characteristics of dairy products since they positively influence texture and organoleptic properties. Besides these, EPS have gained relevant interest for pharmacological and nutraceutical applications due to their biocompatibility, non-toxicity and biodegradability. These bioactive compounds may act as antioxidant, cholesterol-lowering, antimicrobial and prebiotic agents. This review provides an overview of exopolysaccharide-producing LAB, with an insight on the factors affecting EPS production, their dairy industrial applications and health benefits.

Fermentation processes have been used for centuries for food production and preservation. Besides the contribution of fermentation to food quality, recently, scientific interest in the beneficial nature of fermented foods as a reservoir of probiotic candidates is increasing. Fermented food microbes are gaining attention for their health-promoting potential and for being genetically related to human probiotic bacteria. Among them, Lactiplantibacillus ( Lpb .) plantarum strains, with a long history in the food industry as starter cultures in the production of a wide variety of fermented foods, are being investigated for their beneficial properties which are similar to those of probiotic strains, and they are also applied in clinical interventions. Food-associated Lpb. plantarum showed a good adaptation and adhesion ability in the gastro-intestinal tract and the potential to affect host health through various beneficial activities, e.g., antimicrobial, antioxidative, antigenotoxic, anti-inflammatory and immunomodulatory, in several in vitro and in vivo studies. This review provides an overview of fermented-associated Lpb. plantarum health benefits with evidence from clinical studies. Probiotic criteria that fermented-associated microbes need to fulfil are also reported.

Background and Aims: Probiotics can support the body's systems in fighting viral infections. This review is aimed to focus current knowledge about the use of probiotics as adjuvant therapy for COVID-19 patients., Methods: We performed an extensive research using the PubMed-LitCovid, Cochrane Library, Embase databases, and conducting manual searches on Google Scholar, Elsevier Connect, Web of Science about this issue., Results: We have found several papers reporting data about the potential role of probiotics as well as contrasting experimental data about it., Conclusions: Most data show good results demonstrating that probiotics can play a significant role in fighting SARS-CoV-2 infection, also compared with their use in the past for various diseases. They seem effective in lowering inflammatory status, moreover in patients with chronic comorbidities such as cancer and diabetes, improving clinical outcomes., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Food-associated Lactiplantibacillus plantarum (Lpb. plantarum) strains, previously classified as Lactobacillus plantarum, are a promising strategy to face intestinal inflammatory diseases. Our study was aimed at clarifying the protective role of food-borne Lpb. plantarum against inflammatory damage by testing the scavenging microbial ability both in selected strains and in co-incubation with normal mucosa intestinal cells (NCM460). Here, we show that Lpb. plantarum endure high levels of induced oxidative stress through partially neutralizing reactive oxygen species (ROS), whereas they elicit their production when co-cultured with NCM460. Moreover, pre-treatment with food-borne Lpb. plantarum significantly reduce pro-inflammatory cytokines IL-17F and IL-23 levels in inflamed NCM460 cells. Our results suggest that food-vehicled Lpb. plantarum strains might reduce inflammatory response in intestinal cells by directly modulating local ROS production and by triggering the IL-23/IL-17 axis with future perspectives on health benefits in the gut derived by the consumption of functional foods enriched with selected strains.

Background: PADI6 is a component of the subcortical maternal complex, a group of proteins that is abundantly expressed in the oocyte cytoplasm, but is required for the correct development of early embryo. Maternal-effect variants of the subcortical maternal complex proteins are associated with heterogeneous diseases, including female infertility, hydatidiform mole, and imprinting disorders with multi-locus imprinting disturbance. While the involvement of PADI6 in infertility is well demonstrated, its role in imprinting disorders is less well established., Results: We have identified by whole-exome sequencing analysis four cases of Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance whose mothers are carriers of PADI6 variants. In silico analysis indicates that these variants result in loss of function, and segregation analysis suggests they act as either recessive or dominant-negative maternal-effect mutations. Genome-wide methylation analysis revealed heterogeneous and extensively altered methylation profiles of imprinted loci in the patients, including two affected sisters, but not in their healthy siblings., Conclusion: Our results firmly establish the role of PADI6 in imprinting disorders. We report loss-of-function maternal-effect variants of PADI6 that are associated with heterogeneous multi-locus imprinting disturbances in the progeny. The rare finding of two siblings affected by Beckwith-Wiedemann syndrome suggests that in some cases, familial recurrence risk of these variants may be high. However, the heterogeneous phenotypes of the other pedigrees suggest that altered oocyte PADI6 function results in stochastic maintenance of methylation imprinting with unpredictable consequences on early embryo health.

Background and Aim of the Work: COVID-19 is a current global pandemic. However, comprehensive global data analyses for its healthcare management are lacking., Methods: In this study we have researched through published scientific articles and international health care  guidelines to find out actually about our knowledge for this new pandemic from SARS-CoV-2 and related COVID-19 disease that emerged from December 2019 in China in order to better manage this health emergency., Results: The pathogens represented by microorganisms (bacteria, mycetes or viruses) show their effect after days and are responsible for epidemics/pandemics as dangerous as the greater their possibility of transmission, especially by inhalation, and therefore their infectivity., Conclusions: The appearance of new pathogenic viruses for humans such as the COVID -19, which previously were found only in the animal world occurs through the spillover (is the third documented of an animal coronavirus to humans), it is thought that it could also be the same also for the origin of this virus. Furthermore, the trend of this pandemic in one of the countries most affected by Italy after China was also considered.

KPC-producing Klebsiella pneumonia (KPC-Kp) represents a major therapeutic challenge in critically ill patients. Ceftazidime-avibactam (CAZ-AVI) is a new effective drug against KPC-Kp but, due to emerging resistant strains during monotherapy, the association with a second antibiotic has been advocated. Therefore, intravenous fosfomycin may be a possible choice for combination therapy. The aim of this study was to evaluate the in vitro susceptibility of CAZ-AVI alone and in combination with fosfomycin and carbapenems against KPC-Kp clinical isolates by E-test method. The combination of CAZ-AVI with carbapenems showed synergistic activity, whereas with fosfomycin showed addictive activity, suggesting that fosfomycin may be a carbapenem-sparing strategy in antimicrobial stewardship programs.

Lactic acid bacterium, Lactobacillus plantarum, has been applied, for centuries, for food and drink fermentations. Given the benefits associated with fermented products, Lb. plantarum strains have captured considerable industrial and scientific interest, so that they are included as fundamental components of functional foods. Indeed, some strains are marketed as probiotics. In the present study, food- and gut-associated Lb. plantarum isolates were genetically characterized by multilocus sequence typing (MLST) and phenotypically characterized for properties that could influence their probiotic potential. MLST and phylogenetic analysis stratified 22 Lb. plantarum isolates into six lineages. The isolates were further phenotypically characterized by an in vitro assay to assess their potential gut community influence via a limited number of assays including acidification activity, strain displacement activity and their intrinsic range of antibiotic resistance. Given growing recognition of the benefits of fermented foods, and the prevalence of Lb. plantarum in these applications, this study highlights analysis of a subset of preliminary important strain-specific features. These features are of interest to all stakeholders, to inform isolate comparison and selection for current functional food associations, and that can serve as a basis for future strain and food-microbe fermentation product development., (© FEMS 2020.)

Aim: The aim of the present study was to evaluate the prevalence of HPV infection in oral leukoplakia, specifying the HPV genotypes eventually involved. We also compared the micro-biopsy and brushing HPV detecting efficacy., Materials and Methods: Consecutive patients with a presumptive diagnosis of oral leukoplakia were enrolled. Demographical, behavioral data (smoking, alcohol) and lesion features were recorded. Each patient underwent a brushing procedure, performed with a cytobrush rubbed on the lesion, and then a biopsy was performed. The brushing and micro-biopsy specimens were both analyzed with the HPV 28 Anyplex II Seegene RT-PCR. The prevalence of HPV infection was calculated considering the two methods' outcomes separately and then combining both. Cohen's k coefficient was used to assess the agreement between the two methods., Results: Sixty-five patients were enrolled with a mean age of 60 years. The HPV infection prevalence was 17%, decreasing to 5% considering the brushing outcomes alone. The most frequently detected genotypes were 6 (12%), 11 (3%), 42 (3%), and 16 (3%). No statistically significant correlation was found between HPV infection and the variables analyzed, except for smoking and the type of mucosa (p < 0.05). The strength of agreement between cytobrush and micro-biopsy was "fair" (k = 0.384)., Conclusions: The present study showed a low prevalence of HPV infection in oral leukoplakia. The micro-biopsy appeared to be more reliable than brushing in detecting HPV DNA in oral leukoplakia, but the method invasiveness discourages its employ as a screening tool. The importance of HPV in the etiopathogenesis of oral potentially malignant lesions remains unclear; further studies are needed to establish the HPV role in oral leukoplakia., Clinical Relevance: HPV involvement in oral leukoplakia and an effective and appropriate detecting technique are still a debated issue. From this study, the restricted use of brushing did not appear sufficient to assess the presence of HPV infection with PCR techniques in samples obtained from oral leukoplakia.

Antibiotic resistance is an increasingly important global public health issue, as major opportunistic pathogens are evolving toward multidrug- and pan-drug resistance phenotypes. New antibiotics are thus needed to maintain our ability to treat bacterial infections. According to the WHO, carbapenem-resistant Acinetobacter , Enterobactericaeae , and Pseudomonas are the most critical targets for the development of new antibacterial drugs. An automated phenotypic screen was implemented to screen 634 synthetic compounds obtained in-house for both their direct-acting and synergistic activity. Fourteen percent and 10% of the compounds showed growth inhibition against tested Gram-positive and Gram-negative bacteria, respectively. The most active direct-acting compounds showed a broad-spectrum antibacterial activity, including on some multidrug-resistant clinical isolates. In addition, 47 compounds were identified for their ability to potentiate the activity of other antibiotics. Compounds of three different scaffolds (2-quinolones, phenols, and pyrazoles) showed a strong potentiation of colistin, some being able to revert colistin resistance in Acinetobacter baumannii ., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)