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Cauliflower ( Brassica oleraceae L. var. Botrytis Linnaeus) has various health benefits due to its rich bioactive compound content. However, this fresh vegetable faces challenges related to its perishability and short shelf life. This study explores the effect of five drying methods, namely vacuum drying (VD), convective drying (CD), infrared drying (IRD), low-temperature vacuum drying (LTVD) and vacuum freeze-drying (VFD), on the bioactive compounds and health-promoting properties of cauliflower. Analyses of amino acids, hydroxycinnamic acid and its derivatives, glucosinolates, and isothiocyanates, as well as evaluations of their anti-inflammatory, antiproliferative, and neuroprotective properties, were conducted based on these five drying methods. The results revealed that samples treated with VFD and IRD had a higher content of amino acids involved in GSL anabolism. Moreover, VFD samples retained hydroxycinnamic acid derivatives and glucosinolates to a greater extent than other methods. Nonetheless, the CD and VD samples exhibited higher antiproliferative and neuroprotective effects, which were correlated with their high sulforaphane content. Overall, considering the retention of most bioactive compounds from cauliflower and the topical inflammation amelioration induced in mice, VFD emerges as a more satisfactory option.

D2 is a structural and cooperative domain of Thermotoga maritima Arginine Binding Protein, that possesses a remarkable conformational stability, with a denaturation temperature of 102.6°C, at pH 7.4. The addition of potassium thiocyanate causes a significant decrease in the D2 denaturation temperature. The interactions of thiocyanate ions with D2 have been studied by means of isothermal titration calorimetry measurements and molecular dynamics simulations. It emerged that: (a) 20-30 thiocyanate ions interact with the D2 surface and are present in its first solvation shell; (b) each of them makes several contacts with protein groups, both polar and nonpolar ones. The addition of guanidinium thiocyanate causes a marked destabilization of the D2 native state, because both the ions are denaturing agents. However, on adding to the solution containing D2 and guanidinium thiocyanate a stabilizing agent, such as TMAO, sucrose or sodium sulfate, a significant increase in denaturation temperature occurs. The present results confirm that counteraction is a general phenomenon for globular proteins., (© 2024 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)

The SARS-CoV-2 Omicron variant and its sublineages continue to cause COVID-19-associated pediatric hospitalizations, severe disease, and death globally. BNT162b2 and CoronaVac are the main vaccines used in Chile. Much less is known about the Wuhan-Hu-1 strain-based vaccines in the pediatric population compared to adults. Given the worldwide need for booster vaccinations to stimulate the immune response against new Omicron variants of SARS-CoV-2, we characterized the humoral and cellular immune response against Omicron variant BA.1 in a pediatric cohort aged 10 to 16 years who received heterologous vaccination based on two doses of CoronaVac, two doses of CoronaVac (2x) plus one booster dose of BNT162b2 [CoronaVac(2x) + BNT162b2 (1x)], two doses of CoronaVac plus two booster doses of BNT162b2 [CoronaVac(2x) + BNT162b2 (2x)], and three doses of BNT162b2. We observed that the [CoronaVac(2x) + BNT162b2 (2x)] vaccination showed higher anti-S1 and neutralizing antibody titers and CD4 and CD8 T cell immunity specific to the Omicron variant compared to immunization with two doses of CoronaVac alone. Furthermore, from all groups tested, immunity against Omicron was highest in individuals who received three doses of BNT162b2. We conclude that booster vaccination with BNT162b2, compared to two doses of CoronaVac alone, induces a greater protective immunity.

Propolis is a complex mixture formed from exudates that bees collect from plants and then mix with beeswax and their own salivary enzymes. Chilean propolis is characterized by the presence of phenolic compounds, which are considered responsible for the biological activities. The endemic species Escallonia pulverulenta (Ruiz and Pav.) Pers. [Escalloniaceae] is a recognized source of exudate to produce propolis. This study reports for the first time the chemical profile and antibacterial activity of E. pulverulenta exudate and leaves, as well as two samples of Chilean propolis. Palynological and morphological analysis showed the presence of E. pulverulenta as one of the main species in the propolis samples. UPLC-MS/MS analyses enabled the identification of phenolic acids in the leaves and in the propolis. Conversely, flavonoids are mainly present in exudates and propolis. Quercetin is the most abundant flavonol in the exudate, with similar concentrations in the propolis samples. Nevertheless, the main compound present in both samples of propolis was the flavanone pinocembrin. The antibacterial results obtained for exudate and propolis have shown a similar behavior, especially in the inhibition of Streptococcus pyogenes . These results show the importance of the exudates collected by the bees in the chemical composition and antibacterial capacity of propolis.

Rolando Toro's Biodanza (SRT) is a therapeutic strategy that uses movement, music, and emotions to induce integrative living experiences. The present study aims to explore the efficacy of a three-month SRT intervention on motor, cognitive, and behavioral symptoms in patients with Parkinson's disease (PD). This study employed a randomized between-group design. Twenty-eight non-demented PD patients were enrolled in this study. Out of these, fourteen patients were assigned to the active treatment group using the Biodanza SRT system and fourteen to the untreated control group. The study group attended 2 h SRT classes once a week, completing twelve lessons in twelve weeks. All patients underwent: (i) a neurological examination to measure the severity of motor symptoms, balance, mobility, and risk of falls, and (ii) a neuropsychological battery to assess cognitive status, apathy, depressive symptomatology, and perceived quality of life (QoL), at study entry (T0) and at twelve weeks (T1, end of dance training). At T1, we observed a significant improvement in motor (i.e., severity of motor symptoms and balance) and cognitive parameters (i.e., working memory and delayed verbal memory) in all treated patients compared with the controls. Furthermore, a significant improvement in the social support dimension was found in all treated patients compared to the controls. A trend toward increased apathy was found in untreated patients at T1. The three-month Biodanza intervention significantly ameliorated the motor parameters of PD patients, with a parallel improvement in cognitive and QoL status. Hence, Biodanza intervention can, in the short term, represent a useful personalized medical intervention for the management of Parkinson's disease.

Tuberculosis (TB) is the leading global cause of death f rom an infectious bacterial agent. Therefore, limiting its epidemic spread is a pressing global health priority. The chaperone-like protein HtpG of M. tuberculosis (Mtb) is a large dimeric and multi-domain protein with a key role in Mtb pathogenesis and promising antigenic properties. This dual role, likely associated with the ability of Heat Shock proteins to act both intra- and extra-cellularly, makes HtpG highly exploitable both for drug and vaccine development. This review aims to gather the latest updates in HtpG structure and biological function, with HtpG operating in conjunction with a large number of chaperone molecules of Mtb. Altogether, these molecules help Mtb recovery after exposure to host-like stress by assisting the whole path of protein folding rescue, from the solubilisation of aggregated proteins to their refolding. Also, we highlight the role of structural biology in the development of safer and more effective subunit antigens. The larger availability of structural information on Mtb antigens and a better understanding of the host immune response to TB infection will aid the acceleration of TB vaccine development.

The aim of this work is to describe the effect of convective drying (CD), vacuum drying (VD), infrared drying (IRD), low-temperature vacuum drying (LTVD) and freeze drying (FD) on bio-compound retention of red cabbage and its beneficial health properties. The total phenolics content (TPC), flavonoids (TFC), anthocyanin (TAC) and glucosinolates (TGC) were determined by spectrophotometry. The profiles of phenolic acids, amino acids and fatty acids were determined by HPLC-UV-DAD, LC-DAD and GC-FID, respectively. Antioxidant potential was verified by DPPH and ORAC assays. The antiproliferative activity was measured in the human gastric cell line (AGS). Anti-inflammatory activity was evaluated by phorbol 12-myristate 13-acetate and arachidonic acid models. VD showed high values of TPC = 11.89 ± 0.28 mg GAE/g d.m.; TFC = 11.30 ± 0.9 mg QE/g d.m.; TAC = 0.265 ± 0.01 mg Cya3glu/g d.m.; and TGC = 51.15 ± 3.31 µmol SE/g d.m. Caffeic acid, ferulic acid and sinapic acid were identified. The predominant amino acid and fatty acid were glutamic acid and γ-linolenic acid, respectively. The antioxidant potential was dependent on drying methods for both DPPH and ORAC assays. Dried red cabbage extracts showed clear anti-inflammatory and antiproliferative activity. The dehydration process is an alternative for the retention of bio-compounds and health-promoting properties of red cabbage.

Objective: To evaluate the qualitative and quantitative alterations of bone tissue in patients with early-stage Parkinson's disease (PD) and to measure the associations between bone mineral density (BMD), trabecular bone score (TBS) and physical performance., Methods: This case-control study enrolled patients with early-stage PD and age-matched controls. BMDs for the left femoral neck (L-FN) and lumbar spine (LS) were measured. Bone microarchitecture for the LS was determined using TBS. Muscle performance was assessed using the short physical performance battery (SPPB). Patients and controls were stratified in two groups based on the SPPB score: a poor performance group (SPPB score ≤8) and high performance group (SPPB > 8)., Results: This study included 26 patients: 13 in the PD group and 13 age-matched controls. The mean ± SD BMD results in the PD group were: L1-L4 BMD = 0.935 ± 0.183 g/cm 2 ; L-FN BMD = 0.825 ± 0.037 g/cm 2 ; with bone microarchitecture degraded in four patients and partially degraded in three patients. TBS was significantly different in the patients with PD stratified according to SPPB. Among the controls, there was a significant difference in body mass index between the two SPPB groups., Conclusion: TBS might identify bone involvement earlier than BMD in the initial stages of PD., Competing Interests: Declaration of conflicting interestThe authors declare that there are no conflicts of interest.

Marine invertebrates are a traditional source of natural products with relevant biological properties. Tunicates are soft-bodied, solitary or colonial, sessile organisms that provide compounds unique in their structure and activity. The aim of this work was to investigate the chemical composition of the ascidian Cystodytes dellechiajei , selected on the basis of a positive result in biological screening for ligands of relevant receptors of the innate immune system, including TLR2, TLR4, dectin-1b, and TREM2. Bioassay-guided screening of this tunicate extract yielded two known pyridoacridine alkaloids, shermilamine B ( 1 ) and N-deacetylshermilamine B ( 2 ), and a family of methyl-branched cerebrosides ( 3 ). Compounds 2 and 3 showed selective binding to TREM2 in a dose-dependent manner. N-deacetylshermilamine B ( 2 ), together with its acetylated analogue, shermilamine B ( 1 ), was also strongly cytotoxic against multiple myeloma cell lines. TREM2 is involved in immunomodulatory processes and neurodegenerative diseases. N-deacetylshermilamine B ( 2 ) is the first example of a polycyclic alkaloid to show an affinity for this receptor.

Introduction: The D antigen variants are classified as weak, partial, and extremely weak (DEL) and can be differentiated using molecular tests. In Chile, the laboratories of local blood centers do not identify variants of the D antigen, referring them for study to the Reference Laboratory of the Public Health Institute of Chile. So, our aim was to talk about the results of the molecular analysis of variants of the D antigen in samples that had different results in the serological classification., Methods: In the D antigen classification of the Rh system, 479 samples with serological discrepant results were sent for molecular analysis. The Rh phenotype was performed with monoclonal anti-C, anti-c, anti-E, and anti-e antisera by direct agglutination. To find the D antigen, researchers used direct agglutination with monoclonal antisera and indirect antiglobulin testing with the column (gel) agglutination method. Molecular analysis was performed with a polymerase chain reaction with sequence-specific primers (SSP-PCR) and sequencing., Results and Discussion: The presence of D antigen variants was confirmed in 332 samples (69.3%), with an initial discrepancy in serological classification. In this group of discrepant samples, the frequency of weak RhD variants was 66% (219/332), that of extremely weak RhD was 28% (93/332), and that of partial RhD was 6% (20/332). The weak variants type 2 (27.4%), type 3 (8.4%), type 48 (8.4%), and type 1 (8.1%) were the next most prevalent variants after RHD*DEL43 (28%). The ccEe (R2r) phenotype was the most frequently detected (38.4%) and is present in 87% of the RHD*DEL43 samples. The E antigen is associated with the presence of this variant. Our analyses give the first description of D antigen variants in Chile. The most common variants are DEL type (RHD*DEL43) and weak (weak type 2), which are linked to the ccDEe (R2r) phenotype. These findings allow us to characterize the variants of the D antigen in Chile and, according to the obtained data, to design strategies for the management of donors, patients, and pregnant women., 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 Aburto, Zapata, Retamales, Fernández, Barra, Peña, Cárcamo, Saavedra, Sandoval, Orellana and Caamaño.)

Immunogenic Cell Death (ICD) represents a mechanism of enhancing T cell-driven response against tumor cells. The process is enabled by release of damage-associated molecular patterns (DAMPs) and cytokines by dying cells. Based on molecular studies and clinical marker assessment, ICD can be a new target for cancer chemotherapy hitherto restricted to a few conventional anticancer drugs. In view of the development of small molecules in targeted cancer therapy, we reported the preliminary evidence on the role of the natural product lepadin A (1) as a novel ICD inducer. Here we describe the ICD mechanism of lepadin A (1) by proving the translocation of the protein calreticulin (CRT) to the plasma membrane of human A2058 melanoma cells. CRT exposure is an ICD marker in clinical studies and was associated with the activation of the intrinsic apoptotic pathway in A2058 cells with lepadin A (1). After the treatment, the tumour cells acquired the ability to activate dendritic cells (DCs) with cytokine release and costimulatory molecule expression that is consistent with a phenotypic profile committed to priming T lymphocytes via a CD91-dependent mechanism. The effect of lepadin A (1) was dose-dependent and comparable to the response of the chemotherapy drug doxorubicin (2), a well-established ICD inducer., (© 2023. Kunming Institute of Botany, CAS.)

This review article provides an exhaustive survey on experimental investigations regarding the thermal stability assessment of polymers and polymer-based composites intended for applications in the aeronautical and space fields. This review aims to: (1) come up with a systematic and critical overview of the state-of-the-art knowledge and research on the thermal stability of various polymers and composites, such as polyimides, epoxy composites, and carbon-filled composites; (2) identify the key factors, mechanisms, methods, and challenges that affect the thermal stability of polymers and composites, such as the temperature, radiation, oxygen, and degradation; (3) highlight the current and potential applications, benefits, limitations, and opportunities of polymers and composites with high thermal stability, such as thermal control, structural reinforcement, protection, and energy conversion; (4) give a glimpse of future research directions by providing indications for improving the thermal stability of polymers and composites, such as novel materials, hybrid composites, smart materials, and advanced processing methods. In this context, thermal analysis plays a crucial role in the development of polyimide-based materials for the radiation shielding of space solar cells or spacecraft components. The main strategies that have been explored to improve the processability, optical transparency, and radiation resistance of polyimide-based materials without compromising their thermal stability are highlighted. The combination of different types of polyimides, such as linear and hyperbranched, as well as the incorporation of bulky pendant groups, are reported as routes for improving the mechanical behavior and optical transparency while retaining the thermal stability and radiation shielding properties. Furthermore, the thermal stability of polymer/carbon nanocomposites is discussed with particular reference to the role of the filler in radiation monitoring systems and electromagnetic interference shielding in the space environment. Finally, the thermal stability of epoxy-based composites and how it is influenced by the type and content of epoxy resin, curing agent, degree of cross-linking, and the addition of fillers or modifiers are critically reviewed. Some studies have reported that incorporating mesoporous silica micro-filler or microencapsulated phase change materials (MPCM) into epoxy resin can enhance its thermal stability and mechanical properties. The mesoporous silica composite exhibited the highest glass transition temperature and activation energy for thermal degradation among all the epoxy-silica nano/micro-composites. Indeed, an average activation energy value of 148.86 kJ/mol was recorded for the thermal degradation of unfilled epoxy resin. The maximum activation energy range was instead recorded for composites loaded with mesoporous microsilica. The EMC-5p50 sample showed the highest mean value of 217.6 kJ/mol. This remarkable enhancement was ascribed to the polymer invading the silica pores and forging formidable interfacial bonds.

Low-temperature vacuum drying (LTVD) has shown great potential for drying vegetables. It could avoid excessive degradations of active compounds with potential therapeutic agents. In this study, the effect on several relevant bioactive compounds, anti-inflammatory activity, and anti-proliferative activity of broccoli ( Brassica oleracea var. italica) were evaluated. Effects of other drying methods, including vacuum drying (VD), convective drying (CD), infrared drying (IRD), and freeze drying (FD), were also comparatively evaluated. The results of all dried samples showed high polyunsaturated fatty acid contents (of up to 71.3%) and essential amino acid contents (of up to 8.63%). The LTVD method stands out above the other drying methods, since it obtained the highest content of total phenols, chlorogenic acid, and ferulic acid. Both the LTVD and CD samples demonstrated high anti-inflammatory and anti-proliferative activities. These CD and LTVD samples were also the most active against the breast carcinoma MDA-MB-23 cell line. Due to the good retention of bioactive compounds via LTVD, the obtained dried broccoli here can be used in a near time as an ingredient for the development of novel natural products with anti-inflammatory and anti-proliferative effects.

Introduction: Severe acute respiratory syndrome virus 2 (SARS-CoV-2) has caused over million deaths worldwide, with more than 61,000 deaths in Chile. The Chilean government has implemented a vaccination program against SARS-CoV-2, with over 17.7 million people receiving a complete vaccination scheme. The final target is 18 million individuals. The most common vaccines used in Chile are CoronaVac (Sinovac) and BNT162b2 (Pfizer-Biotech). Given the global need for vaccine boosters to combat the impact of emerging virus variants, studying the immune response to SARS-CoV-2 is crucial. In this study, we characterize the humoral immune response in inoculated volunteers from Chile who received vaccination schemes consisting of two doses of CoronaVac [CoronaVac (2x)], two doses of CoronaVac plus one dose of BNT162b2 [CoronaVac (2x) + BNT162b2 (1x)], and three doses of BNT162b2 [BNT162b2 (3x)]., Methods: We recruited 469 participants from Clínica Dávila in Santiago and the Health Center Víctor Manuel Fernández in the city of Concepción, Chile. Additionally, we included participants who had recovered from COVID-19 but were not vaccinated (RCN). We analyzed antibodies, including anti-N, anti-S1-RBD, and neutralizing antibodies against SARS-CoV-2., Results: We found that antibodies against the SARS-CoV-2 nucleoprotein were significantly higher in the CoronaVac (2x) and RCN groups compared to the CoronaVac (2x) + BNT162b2 (1x) or BNT162b2 (3x) groups. However, the CoronaVac (2x) + BNT162b2 (1x) and BNT162b2 (3x) groups exhibited a higher concentration of S1-RBD antibodies than the CoronaVac (2x) group and RCN group. There were no significant differences in S1-RBD antibody titers between the CoronaVac (2x) + BNT162b2 (1x) and BNT162b2 (3x) groups. Finally, the group immunized with BNT162b2 (3x) had higher levels of neutralizing antibodies compared to the RCN group, as well as the CoronaVac (2x) and CoronaVac (2x) + BNT162b2 (1x) groups., Discussion: These findings suggest that vaccination induces the secretion of antibodies against SARS-CoV-2, and a booster dose of BNT162b2 is necessary to generate a protective immune response. In the current state of the pandemic, these data support the Ministry of Health of the Government of Chile's decision to promote heterologous vaccination as they indicate that a significant portion of the Chilean population has neutralizing antibodies against SARS-CoV-2., 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 Díaz-Dinamarca, Díaz, Barra, Puentes, Arata, Grossolli, Riveros-Rodriguez, Ardiles, Santelises, Vasquez-Saez, Escobar, Soto, Canales, Díaz, Lamperti, Castillo, Urra, Zuñiga, Ormazabal, Nova-Lamperti, Benítez, Rivera, Cortes, Valenzuela, García-Escorza and Vasquez.)

This study evaluated the effects of different drying methods (freeze drying, vacuum drying, infrared drying, convective drying, and sun drying) on the biological properties of berries from the Chilean murta ( Ugni molinae Turcz) shrub. Physical-chemical properties (proximal composition, dietary fiber, sugars) were determined. Total phenolic content through the method of Folin-Ciocalteau, the profile of phenol compounds was determined by HPLC, and antioxidant potential by DPPH and ORAC assays were also evaluated. The topic anti-inflammatory effect was evaluated by mice´s ear edema, and in vitro anti-tumoral activity was tested by MTT assay. The chemical properties of dried berries differed significantly based on the drying method: freeze-dried murta berries showed increased total phenolic content extracted over fresh and dried samples. In addition, this lyophilized extract stood out in its antioxidant potential, in both assays evaluated (DPPH and ORAC), compared to the other drying methods. Notwithstanding, vacuum- and infrared-dried murta also showed a higher ORAC value. Antioxidant potential was significantly associated with phenolic compounds catechin and pyrogallol, which were the most abundant phenolic compounds present in all samples. The anti-inflammatory activity was most effective under freeze-drying and vacuumdrying conditions. Moreover, vacuum drying and infrared drying best preserved the anti-tumoral effect on cancer cells., 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 reviewer LF-V declared a shared affiliation with the author JL to the handling editor at the time of review., (Copyright © 2023 López, Vega-Gálvez, Ah-Hen, Rodríguez, Quispe-Fuentes, Delporte, Valenzuela-Barra, Arancibia and Zambrano.)

Pain is an underestimated finding in myotonic dystrophy type 1 (DM1). We provide a characterization of pain in terms of functional implications through a multidimensional assessment in patients with DM1, focusing on gender differences. We assessed pain through the Brief Pain Inventory (BPI) and its indexes (the Severity Index (SI) and the Interference Index (II)), balance/gait (the Tinetti Performance-Oriented Mobility Assessment (POMA)), functional abilities (the Functional Independence Measure (FIM)), and fatigue (the Fatigue Severity Scale (FSS)). We divided our sample into a mild (<4) and a moderate-severe group (≥4) based on BPI indexes. A between-group analysis was performed. We recruited 23 males and 22 females with DM1. A statistically significant difference was found for the FSS and the BPI-SI ≥ 4, and for all outcomes in the BPI-II ≥ 4 ( p ≤ 0.003). In the female group, all outcomes except for the FIM were statistically significantly worse ( p ≤ 0.004). Dividing our sample into four groups based on gender and the BPI, a statistically significant difference was found for FSS between the two groups with BPI-II ≥ 4 (with worsen score in the female one) ( p < 0.002). Pain in DM1 patients is highly reported and gender related, with increased fatigue and poor balance/gait in the female group.

Introduction: Sulfavant A (SULF A) is a synthetic derivative of naturally occurring sulfolipids. The molecule triggers TREM2-related maturation of dendritic cells (DCs) and has shown promising adjuvant activity in a cancer vaccine model., Methods: the immunomodulatory activity of SULF A is tested in an allogeneic mixed lymphocyte reaction (MLR) assay based on monocyte-derived dendritic cells and naïve T lymphocytes from human donors. Flow cytometry multiparametric analyses and ELISA assays were performed to characterize the immune populations, T cell proliferation, and to quantify key cytokines., Results: Supplementation of 10 µg/mL SULF A to the co-cultures induced DCs to expose the costimulatory molecules ICOSL and OX40L and to reduce release of the pro-inflammatory cytokine IL-12. After 7 days of SULF A treatment, T lymphocytes proliferated more and showed increased IL-4 synthesis along with downregulation of Th1 signals such as IFNγ, T-bet and CXCR3. Consistent with these findings, naïve T cells polarized toward a regulatory phenotype with up-regulation of FOXP3 expression and IL-10 synthesis. Flow cytometry analysis also supported the priming of a CD127-/CD4+/CD25+ subpopulation positive for ICOS, the inhibitory molecule CTLA-4, and the activation marker CD69., Discussion: These results prove that SULF A can modulate DC-T cell synapse and stimulate lymphocyte proliferation and activation. In the hyperresponsive and uncontrolled context of the allogeneic MLR, the effect is associated to differentiation of regulatory T cell subsets and dampening of inflammatory signals., 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 Barra, Gallo, Carbone, Ziaco, Dell’Isola, Affuso, Manzo, Nuzzo, Fioretto, D’Ippolito, De Palma and Fontana.)

Tuberculosis (TB) is still the leading global cause of death from an infectious bacterial agent. Limiting tuberculosis epidemic spread is therefore an urgent global public health priority. As stated by the WHO, to stop the spread of the disease we need a new vaccine, with better coverage than the current Mycobacterium bovis BCG vaccine. This vaccine was first used in 1921 and, since then, there are still no new licensed tuberculosis vaccines. However, there is extremely active research in the field, with a steep acceleration in the past decades, due to the advance of technologies and more rational vaccine design strategies. This review aims to gather latest updates in vaccine development in the various clinical phases and to underline the contribution of Structural Vaccinology (SV) to the development of safer and effective antigens. In particular, SV and the development of vaccine adjuvants is making the use of subunit vaccines, which are the safest albeit the less antigenic ones, an achievable goal. Indeed, subunit vaccines overcome safety concerns but need to be rationally re-engineered to enhance their immunostimulating effects. The larger availability of antigen structural information as well as a better understanding of the complex host immune response to TB infection is a strong premise for a further acceleration of TB vaccine development.

In this study, vacuum drying (VD) was employed as an approach to protect the bioactive components of and produce dried broccoli powders with a high biological activity. To achieve these goals, the effects of temperature (at the five levels of 50, 60, 70, 80 and 90 °C) and constant vacuum pressure (10 kPa) were evaluated. The results show that, with the increasing temperature, the drying time decreased. Based on the statistical tests, the Brunauer-Emmett-Teller (BET) model was found to fit well to sorption isotherms, whereas the Midilli and Kucuk model fit well to the drying kinetics. VD has a significant impact on several proximate composition values. As compared with the fresh sample, VD significantly reduced the total phenol, flavonoid and glucosinolate contents. However, it was shown that VD at higher temperatures (80 and 90 °C) contributed to a better antioxidant potential of broccoli powder. In contrast, 50 °C led to a better antimicrobial and neuroprotective effects, presumably due to the formation of isothiocyanate (ITC). Overall, this study demonstrates that VD is a promising technique for the development of extracts from broccoli powders that could be used as natural preservatives or as a neuroprotective agent.

Background: Since the 1980s, cancer research has focused primarily on developing new therapeutic agents targeting DNA alterations rather than understanding cancer as an integrated system composed of several modules. In this sense, G-quadruplex (G4) nucleic acids are a promising target for drug development for cancer therapy since they exist in the chromosomal telomeric sequences and the promoter regions of numerous genes. The G4 structures within telomeric DNA can inhibit telomerase activity and prevent the proliferation and immortalization of cancer cells. Furthermore, such G4 systems within the promoter regions of oncogenes can inhibit the transcription and expression of the oncogene., Objective: The rational design of small molecules such as organic ligands and their metal- organic derivative compounds can stabilize G4 structures through different binding modes on several G4 DNA topologies. Metal-based compounds have demonstrated their competitiveness compared to organic molecules to distinguish G4 over the DNA duplex owing to their convenient coordination features, positive charge, and electron density promoted by organic ligand., Results: This article is a comprehensive review of metal compounds G4-binders and their structural features that confer them the ability to recognize G-quartets and stabilize several DNA G4s., Conclusion: This stabilization can be achieved through extended square aromatic surfaces, increased hydrophobicity, different auxiliary ligands, axially coordinated ligands, and the nature of the metal center., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The prevention of hospital-acquired pressure injuries (HAPIs) in children undergoing long-duration surgical procedures is of critical importance due to the potential for catastrophic sequelae of these generally preventable injuries for the child and their family. Long-duration surgical procedures in children have the potential to result in high rates of HAPI due to physiological factors and the difficulty or impossibility of repositioning these patients intraoperatively. We developed and implemented a multi-modal, multi-disciplinary translational HAPI prevention quality improvement program at a large European Paediatric University Teaching Hospital. The intervention comprised the establishment of wound prevention teams, modified HAPI risk assessment tools, specific education, and the use of prophylactic dressings and fluidized positioners during long-duration surgical procedures. As part of the evaluation of the effectiveness of the program in reducing intraoperative HAPI, we conducted a prospective cohort study of 200 children undergoing long-duration surgical procedures and compared their outcomes with a matched historical cohort of 200 children who had undergone similar surgery the previous year. The findings demonstrated a reduction in HAPI in the intervention cohort of 80% (p < 0.01) compared to the comparator group when controlling for age, pathology, comorbidity, and surgical duration. We believe that the findings demonstrate that it is possible to significantly decrease HAPI incidence in these highly vulnerable children by using an evidence-based, multi-modal, multidisciplinary HAPI prevention strategy., (© 2022 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Vaccine development against Tuberculosis is a strong need, given the low efficacy of the sole vaccine hitherto used, the Bacillus Calmette-Guérin (BCG) vaccine. The chaperone-like protein HtpG Mtb of M. tuberculosis is a large dimeric and multi-domain protein with promising antigenic properties. We here used biophysical and biochemical studies to improve our understanding of the structural basis of HtpG Mtb functional role and immunogenicity, a precious information to engineer improved antigens. We showed that HtpG Mtb is a dimeric nucleotide-binding protein and identified the dimerisation interface on the C-terminal domain of the protein. We also showed that the most immunoreactive regions of the molecule are located on the C-terminal and middle domains of the protein, whereas no role is played by the catalytic N-terminal domain in the elicitation of the immune response. Based on these observations, we experimentally validated our predictions in mice, using a plethora of immunological assays. As an outcome, we designed vaccine antigens with enhanced biophysical properties and ease of production, albeit conserved or enhanced antigenic properties. Our results prove the efficacy of structural vaccinology approaches in improving our understanding of the structural basis of immunogenicity, a precious information to engineer more stable, homogeneous, efficiently produced, and effective vaccine antigens., 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 © 2022 Ruggiero, Choi, Barra, Squeglia, Back, Kim and Berisio.)

Objective: The immune response arises from a fine balance of mechanisms that provide for surveillance, tolerance, and elimination of dangers. Sulfavant A (SULF A) is a sulfolipid with a promising adjuvant activity. Here we studied the mechanism of action of SULF A and addressed the identification of its molecular target in human dendritic cells (hDCs)., Methods: Adjuvant effect and immunological response to SULF A were assessed on DCs derived from human donors. In addition to testing various reporter cells, target identification and downstream signalling was supported by a reverse pharmacology approach based on antibody blocking and gene silencing, crosstalk with TLR pathways, use of human allogeneic mixed lymphocyte reaction., Results: SULF A binds to the Triggering Receptor Expressed on Myeloid cells-2 (TREM2) and initiates an unconventional maturation of hDCs leading to enhanced migration activity and up-regulation of MHC and co-stimulatory molecules without release of conventional cytokines. This response involves the SYK-NFAT axis and is compromised by blockade or gene silencing of TREM2. Activation by SULF A preserved the DC functions to excite the allogeneic T cell response, and increased interleukin-10 release after lipopolysaccharide stimulation., Conclusion: SULF A is the first synthetic small molecule that binds to TREM2. The receptor engagement drives differentiation of an unprecedented DC phenotype (homeDCs) that contributes to immune homeostasis without compromising lymphocyte activation and immunogenic response. This mechanism fully supports the adjuvant and immunoregulatory activity of SULF A. We also propose that the biological properties of SULF A can be of interest in various physiopathological mechanisms and therapies involving TREM2., (© 2022. The Author(s).)

Coronaviruses, including SARS-CoV-2 (the etiological agent of the current COVID-19 pandemic), rely on the surface spike glycoprotein to access the host cells, mainly through the interaction of their receptor-binding domain (RBD) with the human angiotensin-converting enzyme 2 (ACE2). Therefore, molecular entities able to interfere with the binding of the SARS-CoV-2 spike protein to ACE2 have great potential to inhibit viral entry. Starting from the available structural data on the interaction between SARS-CoV-2 spike protein and the host ACE2 receptor, we engineered a set of soluble and stable spike interactors, here denoted as S-plugs. Starting from the prototype S-plug, we adopted a computational approach by combining stability prediction, associated to single-point mutations, with molecular dynamics to enhance both S-plug thermostability and binding affinity to the spike protein. The best developed molecule, S-plug3, possesses a highly stable α-helical con-formation (with melting temperature Tm of 54 °C) and can interact with the spike RBD and S1 domains with similar low nanomolar affinities. Importantly, S-plug3 exposes the spike RBD to almost the same interface as the human ACE2 receptor, aimed at the recognition of all ACE2-accessing coronaviruses. Consistently, S-plug3 preserves a low nanomolar dissociation constant with the delta B.1.617.2 variant of SARS-CoV-2 spike protein (K D = 29.2 ± 0.6 nM). Taken together, we provide valid starting data for the development of therapeutical and diagnostic tools against coronaviruses accessing through ACE2.

Several studies have shown that T-cells might be involved in pathophysiology of acute coronary syndromes (ACS). Tissue factor (TF) plays a key role in ACS. Many evidences have indicated that some statins reduce TF expression in several cell types. However, literature about rosuvastatin and TF and about statins effects on T-cells is still scanty. Colchicine is an anti-inflammatory drug recently proven to have beneficial effects in ACS via unknown mechanisms. This study investigates the effects of colchicine and rosuvastatin on TF expression in oxLDL-activated T-cells. T-cells, isolated from buffy coats of healthy volunteers, were stimulated with oxLDL (50 µg/dL). T-cells were pre-incubated with colchicine (10 µM) or rosuvastatin (5 µM) for 1 h and then stimulated with oxLDL (50 μg/mL). TF gene (RT-PCR), protein (western blot), surface expression (FACS) and procoagulant activity (FXa generation assay) were measured. NF-κB/IκB axis was examined by western blot analysis and translocation assay. Colchicine and rosuvastatin significantly reduced TF gene, and protein expression and procoagulant activity in oxLDL stimulated T-cells. This effect was associated with a significant reduction in TF surface expression as well as its procoagulant activity. These phenomena appear modulated by drug effects on the transcription factor NF-kB. Rosuvastatin and colchicine prevent TF expression in oxLDL-stimulated T-cells by modulating the NF-κB/IκB axis. Thus, we speculate that this might be another mechanism by which these drugs exert benefic cardiovascular effects., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Natural products and their synthetic analogs and derivatives are a traditional source of bioactive molecules with potential development as drug candidates. In this context, Marine Natural Products (MNPs) represent a rich reservoir of diverse molecular skeletons with potential pharmacological activity that, so far, has been mostly explored in cancer and infectious diseases. Starting from the development of a novel bioassay-guided screening platform for immunomodulatory compounds from an in-house MNPs library, we report the identification of the alkaloid lepadin A as a new model compound for immune-based anticancer activity with characteristics that suggest a possible mechanism as Immunogenic Cell Death inducer. The work describes the molecular-based bioprospecting in the Gulf of Naples together with the bioassay-guided fractionation, the chemical characterization of the alkaloid, and the biological activity in mouse dendritic cells (D1).