Search Results (262)

Phytate, an antinutritional molecule in poultry feed, can be degraded by applying phytase, but its use in low- and middle-income countries is often limited due to importation instead of local production. Here, inexpensive raw materials were used to optimize the production of a thermostable phytase from an indigenous strain of Bacillus subtilis SP11 that was isolated from a broiler farm in Dhaka. SP11 was identified using 16s rDNA and the fermentation of phytase was optimized using a Plackett–Burman design and response surface methodology, revealing that three substrates, including the raw material mustard meal (2.21% w/v), caused a maximum phytase production of 436 U/L at 37 °C and 120 rpm for 72 h, resulting in a 3.7-fold increase compared to unoptimized media. The crude enzyme showed thermostability up to 80 °C (may withstand the feed pelleting process) with an optimum pH of 6 (near pH of poultry small-intestine), while retaining 96% activity at 41 °C (the body temperature of the chicken). In vitro dephytinization demonstrated its applicability, releasing 978 µg of inorganic phosphate per g of wheat bran per hour. This phytase has the potential to reduce the burden of phytase importation in Bangladesh by making local production and application possible, contributing to sustainable poultry nutrition. Full article

Furfural is a fascinating bio-based platform molecule that can be converted into useful cyclic compounds, among others. In this work, the hydrogenative rearrangement-dehydration of furfural towards cyclopentanone using a commercially available Pt/C catalyst was investigated in terms of its reaction performance to assess its feasibility as an industrial process. However, acquiring an acceptable cyclopentanone yield proved very difficult, and the reaction was constrained by unforeseen parameters, such as the relative liquid volume in the reactor and the substrate concentration. Most strikingly, the sacrificial formation of furanoic oligomers that precipitated onto the catalyst’s surface was a troublesome key factor that mediated the product’s selectivity versus the carbon mass balance. By applying a biphasic water–toluene solvent system, the yield of cyclopentanone was somewhat improved to a middling 59%, while tentatively positive distributions of reaction components over these solvent phases were observed, which could be advantageous for anticipated down-stream processing. Overall, the sheer difficulty of controlling this one-pot cascade transformation towards a satisfactory product output under rather unfavorable reaction parameters renders it unsuitable for industrial process development, and a multi-step procedure for this chemical transformation might be considered instead. Full article

Background/Objectives: Vaccine immunogenicity is often suboptimal in vulnerable populations such as the elderly, infants, and individuals in low- and middle-income countries. One contributing factor may be pre-existing immunomodulatory conditions, including helminth infections. This study investigates the impact of Fasciola hepatica (F. hepatica) derived molecules on the early humoral response to the COVID-19 mRNA vaccine Comirnaty^® in a mouse model. Methods: BALB/c mice were pretreated with a F. hepatica protein extract (FH) or complete Freund’s adjuvant (CFA) prior to vaccination. Cytokine production and antibody responses were assessed at 0, 14, and 21 days post-vaccination (dpv) through serum analysis and ex vivo splenocyte stimulation with the SARS-CoV-2 receptor-binding domain (RBD) or LPS. Results: At 0 dpv, FH-treated mice showed increased serum IL-10, while CFA treatment induced IL-12. FH- but not CFA-treated splenocytes secreted IL-10 upon RBD or LPS stimulation. At 21 dpv, FH-treated mice lacked IFN-γ production but maintained IL-10 and showed elevated IL-4, consistent with a Th2-skewed profile. Although total anti-RBD IgG levels were similar between groups, FH-treated mice exhibited reduced IgG avidity and a higher IgG1/IgG2 ratio. CFA-treated mice showed delayed avidity maturation. Conclusions: Prior exposure to F. hepatica antigens can modulate the early immune response to Comirnaty^®, affecting both cellular activation and antibody quality. This altered response may reflect a reduced early protective capacity of the vaccine, which might need to be considered when designing or evaluating vaccination strategies using mRNA vaccines in helminth-endemic regions. Full article

Background: Epidemiological research has shown that regular walnut (from Juglans regia L.) consumption is associated with a reduced risk of cardiovascular disease (CVD), potentially attributable to their antioxidant and anti-inflammatory properties. The vascular cellular adhesion molecule-1 (VCAM-1), a protein upregulated in CVD, has been previously examined in relation to walnut consumption. However, the clinical findings regarding the effects of walnuts on endothelial function among middle-aged individuals susceptible to metabolic syndrome (MetS) remain inconclusive. Objective: This study examined the effects of daily walnut consumption over a four-week period on cardiometabolic parameters (lipid and glycemic profiles, as well as soluble VCAM-1 levels) and anthropometric measurements in middle-aged individuals with at least one altered MetS parameter and no medication. Methods: In a randomized controlled cross-over trial, 22 eligible Caucasian participants (48.81 ± 4.3 years) were selected and randomly assigned to receive either 45 g of walnuts per day or no walnuts within a controlled diet. There were two 28-day intervention periods, with a one-month washout period in between. Clinical and biochemical evaluations were conducted at the beginning and end of each intervention period. Results: A total of 20 participants completed the intervention and were analyzed, with walnuts being well tolerated. A significant decrease in waist circumference (p = 0.049) and a slight change in fasting blood glucose (p = 0.089) were noted following walnut intake. Conclusions: Short-term (4 weeks) dietary supplementation with walnuts resulted in a statistically significant reduction in waist circumference while not impacting the overall health status of participants. Longer-term studies are necessary to investigate the benefits of daily walnut consumption and its impact on the onset and development of MetS in this age group. Full article

NAD⁺ is a fundamental molecule participating as a redox cofactor in several metabolic reactions and has a neuroprotective role associated with oxidate stress. Despite its critical role, NAD⁺ levels sharply decline with age, contributing to the pathogenesis of aging-related diseases. Supplementation with nicotinamide riboside (NR), also known as a form of vitamin B3, a biochemical precursor of NAD⁺, may replenish this depletion. Background/Objectives: Mounting evidence suggests that dietary supplementation with NR, a form of vitamin B3 and a biochemical precursor of NAD⁺, enhances NAD⁺ bioavailability and prevents the detrimental effects on sleep, cognitive function, mitochondrial function, and insulin sensitivity. However, there is a paucity of studies focused on how NR administration affects sleep patterns. This narrative review summarizes the current state of scientific knowledge on the effects of nicotinamide riboside supplementation on sleep. Results: Pre-clinical studies indicate that NR enhances the performance of the clock genes BMAL1 and PER2, and ameliorates chronic sleep deprivation-induced cognitive impairment, potentially by alleviating oxidative stress and mitochondrial impairment in microglia. NR supplementation also increased REM sleep and reduced NREM sleep by approximately 17%. In human studies, NR improved sleep efficiency in young and middle-aged male individuals with insomnia. It also improved sleep quality and reduced fatigue and drowsiness in older adults. More research is warranted to understand the impacts of NR on sleep for women. Conclusions: NR supplementation is a reliable and effective alternative to boost NAD⁺ levels and may ameliorate sleep patterns. Full article

Senescence in placental cells impacts physiological functions and contributes to pathology. Therefore, we examined biochemical markers of cellular senescence—p38, P-p38, p21, and p53—during pregnancy, at parturition, and in cases of retained fetal membranes. Placentomes were collected from pregnant cows (2nd, 4th, and 5th months of gestation) and parturient cows undergoing cesarean section, categorized as NR or RFM. Samples were separated into maternal and fetal parts and analyzed via WB and ELISA. WB confirmed protein presence, while ELISA showed a significant increase in the concentrations of both p38 and P-p38 in the fetal part in the 5th month of gestation as compared to earlier months. No significant differences were observed in the maternal part across pregnancy and parturition. These findings suggest p38 and P-p38 may be important molecules regulating the normal development of the bovine placenta during middle pregnancy. Further studies are needed to elucidate the mechanisms of their action. Full article

Kidney disease causes the retention of uremic metabolites in blood, which is associated with many comorbidities. Hemodialysis does not properly clear many metabolites, including large, middle-sized, and small protein-bound uremic toxins (PBUTs). Adsorption strategies for metabolite removal require the development of engineered adsorbents with tailored surfaces to increase the binding of desired metabolites. Albumin is uniquely positioned for modifying blood-contacting surfaces to absorb uremic metabolites, as it (i) minimizes non-specific protein adsorption and (ii) binds a range of molecules at Sudlow Sites I and II with different affinities. It is unknown if albumin-modified surfaces retain the adsorption qualities of solution-free albumin, namely, adsorption stability or specificity. Herein, albumin was covalently attached to iron oxide nanoparticles and characterized using multiple methods. Metabolite adsorption was conducted by incubating particles in a model solution of thirty-three uremic metabolites associated with kidney failure. Adsorption efficiency, selectivity, and stability were affected by albumin concentration and incubation time. Metabolite adsorption was found to change with time, and it was more effective on albumin-modified particles than unmodified controls. The findings outlined in this paper are crucial for the design of next-generation advanced blood-contacting materials to enhance dialysis and blood purification for patients with kidney disease. Full article

The lower and middle Carboniferous shale sequences are one of the important potential hydrocarbon source rocks in the piedmont of the southwestern Tarim Basin, China (PSTB). Rock samples were collected from the lower and middle Carboniferous formations on the Kushanhe, Altash, and Aitegou outcrops in the PSTB with the intention of mapping the hydrocarbon molecules within these shale sources and disclosing the relevant geochemical implications. The ratios of Pr/Ph < 1.0 and DBT/P < 0.4 and the enrichment of C₂₃ tricyclic terpanoid indicate that the Carboniferous shale sources were deposited in a reducing and sulfate-poor marine setting with the contribution of terrestrial freshwater. Marine aquatic algae act as the major contributor, resulting in the formation of Type II₁ kerogen. The Carboniferous shale sequences contain abundant diamondoids with 2–4 cages with the predominance of methyldiamantanes, dimethyldiamantanes, and methyltriamantanes. Quantitative extended diamondoid analysis indicates the occurrence of carbonate-rich and carbonate-poor organic facies in the PSTB. Compared to the carbonate-poor facies, the carbonate-rich facies is relatively depleted in C₂₇ diasteranes and rich in gammacerane, C₂₇ regular steranes, and alkylated triamantanes. This indicates that it was deposited in the more salty and stratified water column but with less input of land higher plants. The clay catalysis effects are assumed to be responsible for the discrepancy in steranes and diamondoids. The Carboniferous shale sequences also contain abundant polycyclic aromatic hydrocarbons with 2–5 rings with the predominance of C_0–1-phenanthrenes, chrysenes, and benzofluoranthenes. Thermal maturity parameters associated with polycyclic aromatic hydrocarbons and diamondoids suggest that the Carboniferous shale sources have arrived at the late mature to highly mature stage. This study provides the detailed molecular fingerprints of the lower and middle Carboniferous shale source sequences and explores the underlying geochemical implications. This should be helpful for oil–oil and oil–source correlations and hence petroleum exploration activity in the PSTB. Full article

Diabetic kidney disease (DKD) displays a high prevalence of cardiovascular and cerebrovascular disease. Both the kidney and the brain share common pathogenic mechanisms, such as inflammation, endothelial dysfunction, oxidative stress, and mitochondrial dysfunction. The aim of this study was to establish a potential association of cerebral vessel remodeling and its related functional impairment with biomarkers of inflammation, oxidative stress, and mitochondrial dysfunction in the early stages of DKD in type 2 diabetes mellitus (DM) patients. A cohort of 184 patients and 39 healthy controls was assessed concerning serum and urinary stromal cell-derived factor-1 (SDF-1), P-selectin, advanced oxidation protein products (AOPPs), urinary synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), and N-acetyl-β-(D)-glucosaminidase (NAG). The quantification of the mitochondrial DNA copy number (mtDNA-CN) and nuclear DNA (nDNA) in urine and peripheral blood was conducted using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Using TaqMan tests, the beta-2 microglobulin nuclear gene (B2M) and the cytochrome b (CYTB) gene, which encodes subunit 2 of NADH dehydrogenase (ND2), were evaluated. The MtDNA-CN is the ratio of mitochondrial DNA to nuclear DNA copies, ascertained through the examination of the CYTB/B2M and ND2/B2M ratios. The intima-media thickness (IMT) measurements of the common carotid arteries (CCAs), along with the pulsatility index (PI) and resistivity index (RI) of the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), were obtained through cerebral Doppler ultrasonography (US). Additionally, the breath-holding index (BHI) was also measured by cerebral Doppler US. PI-ICAs, PI-MCAs, CCAs-IMT, RI-MCAs, and RI-ICAs demonstrated direct relationships with SDF-1, P-selectin, AOPPs, urine mtDNA, podocalyxin, synaptopodin, NAG, and KIM-1 while showing indirect correlations with serum mtDNA and the eGFR. In contrast, the BHI had negative correlations with SDF-1, P-selectin, AOPPs, urine mtDNA, synaptopodin, podocalyxin, KIM-1, and NAG while showing direct associations with serum mtDNA and the eGFR. In conclusion, a causative association exists among SDF-1, P-selectin, and AOPPs, as well as mitochondrial dysfunction, in early diabetic kidney disease (DKD) and significant cerebrovascular alterations in patients with type 2 diabetes mellitus and normoalbuminuric DKD, with no neurological symptoms. Full article

Geochemical and isotopic analysis of bitumen lining potsherds from the al-Qusur monastery (second half of the 7th c. CE and the middle of the 9th c. CE), at the central part of Failaka Island (Kuwait Bay), confirms the presence of two distinct compositional categories that can be matched to contemporary sources from two different areas of Iran: the Kermanshah province on one side, and the Khuzestan–Fars–Busher provinces on the other side. Potsherds comprise different types: TORP-S amphorae, TORP-C amphorae, SPORC storage jar, turquoise alkaline-glazed jar (TURQ.T), and CREAC jar. There is no relationship between the type of potsherd and the origin of bitumen. The bitumen coating SPORC jar, first identified as a kind of juice strainer to filter the «garum-like juice», was examined in greater details to try to identify traces of fish sauce mentioned in the Arabic kitchen books as ‘murri’, and quite similar to the Roman garum. The mineralogical analysis exhibits the classical minerals of archaeological mixtures (quartz, calcite, dolomite) and no halite. Hydrocarbons, alcohols, and methyl esters show a typical biodegraded bitumen signature but no fatty acids and terpenoids. It seems that the bitumen matrix has not adsorbed any molecules from the presumed «garum» filtered in the basin. Full article

Because of the involvement of π-electron cyclic constituents in their side chains, the so-called aromatic residues give rise to a number of strong, narrow, and well-resolved lines spread over the middle wavenumber (1800–600 cm⁻¹) region of the Raman spectra of peptides and proteins. The number of characteristic aromatic markers increases with the structural complexity (Phe → Tyr → Trp), herein referred to as (F_i = 1, …, 6) in Phe, (Y_i = 1, …, 7) in Tyr, and (W_i = 1, …, 8) in Trp. Herein, we undertake an overview of these markers through the analysis of a representative data base gathered from the most structurally simple tripeptides, Gly-Xxx-Gly (where Xxx = Phe, Tyr, Trp). In this framework, off-resonance Raman spectra obtained from the aqueous samples of these tripeptides were jointly used with the structural and vibrational data collected from the density functional theory (DFT) calculations using the M062X hybrid functional and 6-311++G(d,p) atomic basis set. The conformation dependence of aromatic Raman markers was explored upon a representative set of 75 conformers, having five different backbone secondary structures (i.e., β-strand, polyproline-II, helix, classic, and inverse γ-turn), and plausible side chain rotamers. The hydration effects were considered upon using both implicit (polarizable solvent continuum) and explicit (minimal number of 5–7 water molecules) models. Raman spectra were calculated through a multiconformational approach based on the thermal (Boltzmann) average of the spectra arising from all calculated conformers. A subsequent discussion highlights the conformational landscape of conformers and the wavenumber dispersion of aromatic Raman markers. In particular, a new interpretation was proposed for the characteristic Raman doublets arising from Tyr (~850–830 cm⁻¹) and Trp (~1360–1340 cm⁻¹), definitely excluding the previously suggested Fermi-resonance-based assignment of these markers through the consideration of the interactions between the aromatic side chain and its adjacent peptide bonds. Full article

Background: The blood–brain barrier (BBB) plays an important role in regulating homeostasis of the central nervous system (CNS), and it is an obstacle for molecules with a molecular weight higher than 500 Da seeking to reach it, making many drugs ineffective simply because they cannot be delivered to where they are needed. As a result, crossing the BBB remains the rate-limiting factor in brain drug delivery during the treatment of brain diseases, specifically tumors such as diffuse intrinsic pontine glioma (DIPG), a highly aggressive pediatric tumor with onset in the pons Varolii, the middle portion of the three contiguous parts of the brainstem, located above the medulla and below the midbrain. Methods: Currently, radiotherapy (RT) relieves DIPG symptoms but chemotherapy drugs do not lead to significant results as they do not easily cross the BBB. Focused ultrasound (FUS) and microbubbles (MBs) can temporarily open the BBB, facilitating radiotherapy and the entry of drugs into the CNS. A patient-derived xenograft DIPG model exposed to high-intensity focalized ultrasound (HIFU) or low-intensity focalized ultrasound (LIFU) combined with MBs was treated with doxorubicin, panobinostat, olaparib, ONC201 (Dordaviprone^®) and anti-PD1. Panobinostat has also been used in children with diffuse midline glioma, a broad class of brain tumors to which DIPG belongs. Results: Preliminary studies were performed using FUS to temporarily open the BBB and allow a milder use of radiotherapy and facilitate the passage of drugs through the BBB. The data collected show that after opening the BBB with FUS and MBs, drug delivery to the CNS significantly improved. Conclusions: FUS associated with MBs appears safe and feasible and represents a new strategy to increase the uptake of drugs in the CNS and therefore enhance their effectiveness. This review reports pre-clinical and clinical studies performed to demonstrate the usefulness of FUS in patients with DIPG treated with some chemotherapy. The papers reviewed were published in PubMed until the end of 2024 and were found using a combination of the following keywords: diffuse intrinsic pontine glioma (DIPG), DIPG H3K27-altered, blood–brain barrier and BBB, focused ultrasound (FUS) and radiotherapy (RT). Full article

As chronic kidney disease (CKD) prevalence rises, optimizing hemodialysis remains essential. While online hemodiafiltration (OL-HDF) is the gold standard, expanded hemodialysis (HDx), i.e., using high-performance dialyzers in standard hemodialysis, remains the most common clinical practice. Medium cutoff (MCO) membranes aim to enhance middle-molecule removal while preserving protein selectivity, although most studies evaluate them in OL-HDF. To this end, this study aims to compare the Xevonta-Hi (B. Braun), a high-flux (HF) polysulfone dialyzer, and the ELISIO-HX (Nipro), an MCO polyethersulfone dialyzer, in standard hemodialysis. In a prospective, observational study, seven stable patients sequentially received treatment with each dialyzer over four weeks. Pre- and post-dialysis levels of small and middle uremic molecules and inflammatory markers—including procalcitonin, prolactin, serum amyloid A, placental growth factor, interleukin-6, haptoglobin, ceruloplasmin, transferrin, prealbumin, and C-reactive protein—were measured. Both dialyzers demonstrated excellent clearance of small and middle molecules, with no significant differences in efficacy. Albumin and total protein losses remained minimal. Moderate reductions in serum amyloid A, placental growth factor, and interleukin-6 were observed, while no significant reductions occurred in the remaining inflammatory markers. These findings support the safety and effectiveness of both MCO and HF dialyzers in standard hemodialysis. Full article

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging zoonotic pathogen with different pathogenesis in humans and camels. The mechanisms behind the higher tolerance of camels to MERS-CoV infection are still unknown. Monocytes are innate myeloid cells that are able, depending on the local stimulation in their microenvironment, to differentiate into different functional subtypes of macrophages with an impact on the adaptive immune response. Several in vitro protocols have been used to induce the differentiation of monocyte-derived macrophages (MDMs) in human and several veterinary species. Such protocols are not available for camel species. In the present study, monocytes were separated from camel blood and differentiated in vitro in the presence of different stimuli into MDM. Camel MDMs generated in the presence of a combined stimulation of monocytes with LPS and GM-CSF resulted in the development of an M1 macrophages phenotype with increased abundance of the antigen-presentation receptor MHCII molecules and a decreased expression of the scavenger receptor CD163. The expression pattern of the cell markers CD163, CD14, CD172a, CD44, and CD9 on MDM generated in the presence of the MERS-CoV S1 protein revealed similarity with M-CSF-induced MDM, suggesting the potential of the MERS-CoV S1 protein to induce an M2 macrophages phenotype. Similarly to the effect of M-CSF, MERS-CoV-S protein-induced MDMs showed enhanced phagocytosis activity compared to non-polarized or LPS/GM-CSF-polarized MDMs. Collectively, our study represents the first report on the in vitro generation of monocyte-derived macrophages (MDMs) in camels and the characterization of some phenotypic and functional properties of camel MDM under the effect of M1 and M2 polarizing stimuli. In addition, the results suggest a polarizing effect of the MERS-CoV S1 protein on camel MDMs, developing an M2-like phenotype with enhanced phagocytosis activity. To understand the clinical relevance of these in vitro findings on disease pathogenesis and camel immune response toward MERS-CoV infection, further studies are required. Full article

Background: Removal of large uraemic toxins is still a challenge. Haemodiafiltration (HDF) has produced some results, although large convective volume, optimal vascular access to increase the blood flow rate and strict water quality management are required. Medium cut-off, high-retention-onset membranes have been recently developed, introducing the concept therapy called expanded haemodialysis (HDx). Furthermore, vitamin E-coated membrane has potential beneficial effects on inflammation and oxidative stress. Methods: A prospective longitudinal multicentre study was conducted for 3 months among 24 chronic haemodialysis patients. Patients were randomly assigned into either HDF with high-flux membrane or HDx with Theranova or ViE-X membrane. The primary goal was to assess albumin loss among the three types of dialyzers. Secondary goals included assessment of depurative efficacy for uraemic toxins and clinical outcomes. Results: Mean albumin loss was significantly higher in patients undergoing HDx with Theranova membrane, without any difference in serum albumin concentration among the three groups. Instantaneous clearance of small and middle molecules was significantly higher in patients undergoing HDF, but we did not find differences in removal ratio and Kt/V. Reduction in the erythropoietin resistance index was observed in patients treated with ViE-X membrane due to their lower dialysis vintage. Conclusions: The higher albumin loss during HDx has no effects on pre-dialysis serum albumin. HDx with Theranova in the presence of lower session length, lower Qb, lower convective dose, and lower instantaneous clearance reached the same dialysis efficacy compared to HDF. Full article