Body Fluids Research Articles

Application of Response Surface Methodology Experimental Design to Optimize Tribological Lubrication Characteristics

Total Knee Replacement (TKR) has become a standard operation for patients with joint disorders. Despite the fact that the number of procedures is increasing all the time, the short service life of implants remains a persistent concern for researchers. Understanding lubrication may aid in explaining tribological processes that lead to replacements that last well into the third decade of service. Likewise, wear and friction in total knee replacement (TKR) components are among the most common causes of implant failure. As a result, this study will evaluate the feasibility of using the polymer Poly Lactic Acid (PLA) for cartilage replacement in Total Knee Replacement (TKR) using plant-based oils as lubricants. Furthermore, the modifier will be added to plant-based oils as an additive to make them analogous to human bodily fluids. The present paper is applying the Box-Behnken design to optimize the performance and mechanical responses of bio-lubricants toward Poly Lactic Acid (PLA) as a tibial insert for cartilage replacement in Total Knee Replacement (TKR). The main objective of this paper is to develop an optimized method for the selection of plant-based oil parameters using Response Surface Methodology (RSM). A three-level three-factor Box-Behnken design (BBD) was used to investigate the interactions between the essential factors comprising load (45 kg to 90 kg), speed (60 rpm, 90 rpm and 360 rpm), and concentration (0ml, 5ml and 10ml) of bio-lubricants to accomplish the indicated prospect of using polymer for cartilage replacement. Canola oil, castor oil, and sunflower seed oil are considered vegetable oils, whereas Hyaluronic Acid (HA) is the friction modifier. The parameters are used to create a Box-Behnken design for predicting lubricant anti-wear qualities stated in terms of coefficient of friction, wear rate and frictional force as determined by the pin-on-disk experimental procedure. As a result, the optimization using RSM successfully interpreted the experimental data, according to the analysis of variance, with coefficients of determination of R2 = 0.91 and adjusted R2 = 0.77. The Coefficient of Friction (CoF) and wear rate were investigated following tribological testing. Castor oil had a lower coefficient of friction than canola and sunflower seed oil, according to the findings. In terms of friction reduction, castor oil surpasses canola and sunflower seed oil.

Overview of human health effects related to glyphosate exposure

Glyphosate is a chemical compound derived from glycine, marketed as a broad-spectrum herbicide, and represents one of the most widely used pesticides in the world. For a long time, it was assumed that glyphosate was harmless, either due to its selective enzymatic acting method on plants, and because commercial formulations were believed to contain only inert chemicals. Glyphosate is widely spread in the environment, the general population is daily exposed to it via different routes, including the consumption of both plant, and non-plant based foods. Glyphosate has been detected in high amounts in workers’ urine, but has been detected likewise in bodily fluids, such as blood and maternal milk, and also in 60%–80% of general population, including children. Considering its massive presence, daily exposure to glyphosate could be considered a health risk for humans. Indeed, in 2015, the IARC (International Agency for Research on Cancer) classified glyphosate and its derivatives in Group 2A, as probable human carcinogens. In 2022, nevertheless, EFSA (European Food Safety Authority) stated that the available data did not provide sufficient evidence to prove the mutagenic/carcinogenic effects of glyphosate. Therefore, the European Commission (EC) decided to renew the approval of glyphosate for another 10 years. The purpose of this review is to examine the scientific literature, focusing on potential risks to human health arising from exposure to glyphosate, its metabolites and its commercial products (e.g., Roundup®), with particular regard to its mutagenic and carcinogenic potential and its effects as endocrine disrupter (ED) especially in the human reproductive system.

Recent Advances of Nipah Virus Disease: Pathobiology to Treatment and Vaccine Advancement.

The zoonotic infection of the Nipah virus (NiV) has yet again appeared in 2023 in Kerala state, India. The virus, which has a mortality rate ranging from about 40 to 70%, has already infected India five times, the first being in 2001. The current infection is the sixth virus outbreak in the Indian population. In 1998, the first NiV infection was noted in one village in Malaysia. After that, outbreaks from other South and Southeast Asian countries have been reported periodically. It can spread between humans through contact with body fluids. Therefore, it is unlikely to generate a new pandemic. However, there is a considerable knowledge gap in the different areas of NiV. To date, no approved vaccines or treatments have been available.Tofulfilthe knowledge gap, the review article provided a detailed overview of the genome and genome-encoded proteins, epidemiology, transmission, pathobiology, immunobiology, diagnosis, prevention and control measures, therapeutics (monoclonal antibodies and drug molecules), and vaccine advancement of the emerging and deadly pathogen. The advanced information will help researchers todevelop safe and effective NiV vaccine and treatment regimens worldwide.

Frequency of exposure incidents in hospital workers before and during the COVID-19 pandemic based on the hospital status and the use of personal protective equipment: a descriptive study with a historical comparison group

BackgroundAn occupational exposure, i.e. exposure incident (EI), is contact with potentially contaminated material that may contain bloodborne pathogens and that occurs during occupational activities inside or outside a health care facility, either during direct work with a patient or during contact with a patient’s body fluids and tissues. This study aimed to compare the frequency of EIs in a university hospital before and during the Coronavirus Disease 2019 (COVID-19) pandemic.MethodsThis was a descriptive study with a historical comparison group conducted at the Dubrava University Hospital (DUH) in Zagreb, Croatia. We compared the frequency of EIs among healthcare and non-healthcare workers before (from March 11, 2018, to March 10, 2020) and during (from March 11, 2020, to March 11, 2022) the COVID-19 pandemic, expressed as the number of EIs per number of hospitalized patients and the total number of hospital activities. We analyzed data based on the status of the hospital (a COVID-19 hospital or not) and the use of personal protective equipment (PPE) as recommended by the World Health Organization.ResultsDuring the total analyzed period, 241 EIs were reported in DUH. Before the pandemic, 128 EIs were reported, compared to 113 during the pandemic. Before the pandemic, 91% of EIs were recorded in healthcare workers, while during the pandemic, 96% of EIs were recorded in healthcare workers. Slightly more EIs were recorded during the period of mixed work form and de-escalation of PPE. The rate of EIs relative to the total number of hospital patients was significantly higher during the pandemic (3.9/1000) than in the pre-pandemic period (2.5/1000). The rate of EIs relative to the total number of hospital activities was significantly higher during the pandemic (0.4/1000) than in the pre-pandemic period (0.2/1000).ConclusionThe rate of EIs relative to the total number of hospitalized patients and the total number of hospital activities in DUH was significantly higher during the pandemic, and the rate of total EIs increased among healthcare workers during the COVID-19 pandemic. The results of this study show that it is necessary to constantly and effectively work on the prevention of EI.

Exploring the interplay of natural products and long non-coding RNAs in colorectal cancer: pathogenesis, diagnosis, and overcoming drug resistance.

Colorectal cancer (CRC) is recognized as one of the most prevalent malignancies, both in terms of incidence and mortality rates. Current research into CRC has shed light on the molecular mechanisms driving its development. Several factors, including lifestyle, environmental influences, genetics, and diet, play significant roles in its pathogenesis. Natural compounds such as curcumin, tanshinone, lycorine, sinomenine, kaempferol, verbascoside, quercetin, berberine, and fisetin have shown great promise in the prevention and treatment of CRC. Research has also highlighted the significance of non-coding RNAs (ncRNAs) as biomarkers and therapeutic targets in CRC. Among these, long non-coding RNAs (lncRNAs) have been found to regulate the transcription of genes involved in cancer. LncRNAs contribute to cancer stem cell (CSC) proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), and chemoresistance. Specific lncRNAs, including GAS5, LNC00337, HOTAIR, TPT1-AS1, cCSC1, BCAR4, TUG1, and Solh2, play crucial roles in these processes. They hold potential as novel biomarkers, detectable in bodily fluids and tissues, and could serve as therapeutic targets due to their involvement in drug resistance and sensitivity. These insights could improve CRC treatment strategies, addressing resistance to chemotherapy and radiotherapy. This review article aims to provide a comprehensive analysis of the current knowledge regarding the effectiveness of natural anti-cancer agents in CRC treatment. Additionally, it offers an in-depth evaluation of lncRNAs in CRC, their role in the disease's progression, and their potential applications in its management.

Differential miRNA Expression Patterns between TallyHo/JngJ Mice and Non-Diabetic SWR/J Mice

Abstract Type 2 diabetes mellitus (T2DM) increases the susceptibility of bone fragility. The underlying mechanisms have, however, remained largely unknown. MicroRNAs (miRNAs) are short single-stranded non-coding RNA molecules with utility as biomarkers due to their easy accessibility and stability in bodily fluids. Here, we aimed to use an unbiased approach to identify miRNAs dysregulated in a polygenic mouse model of T2DM. Genome-wide analysis of miRNAs in serum, bone marrow and bone from the polygenic TallyHo/JngJ (TH) mice, which recapitulate T2DM in humans, was performed. This analysis was compared to the recommended control SWR/J and a strain-matched non-diabetic control (TH-ND). When comparing TH mice with TH-ND using an adjusted P-value (FDR) cut-off of 0.2 to identify differentially expressed miRNAs, mmu-miR-466i-5p and mmu-miR-1195 were found to be up-regulated in both serum and in bone marrow. Dysregulated miRNAs were not found in bone tissue. When comparing TH-ND mice with SWR/J using the same FDR cut-off, mmu-miR-351-5p and mmu-miR-322-3p were upregulated in both bone marrow and serum, while mmu-miR-449a-5p and mmu-miR-6240 were downregulated in bone marrow and serum. Dysregulated miRNAs in bone marrow or cortical bone compared to serum between TH-ND mice and SWR/J were investigated for their cell-type enrichment to identify putative donor cells and their gene target networks. Gene target network analysis revealed genes involved in diabetes-related signaling pathways as well as in diabetic bone disease. Cell-type enrichment analysis identified hsa-miR-449a enriched in immune cells, hsa-miR-592 in hepatocytes and endothelial cells, while hsa-miR-424-3p, hsa-miR-1-3p and hsa-miR-196b-5p were enriched in mesenchymal stem cells and their derived tissues. In conclusion, our comparative miRNA profiling sheds light on differential expression patterns between SWR/J and both subgroups of TH. No differences were observed between TH and TH-ND suggesting the genetical background of SWR/J may be responsible for the change of dysregulated miRNA.

The GFAP proteoform puzzle: How to advance GFAP as a fluid biomarker in neurological diseases.

Glial fibrillary acidic protein (GFAP) is a well-established biomarker of reactive astrogliosis in the central nervous system because of its elevated levels following brain injury and various neurological disorders. The advent of ultra-sensitive methods for measuring low-abundant proteins has significantly enhanced our understanding of GFAP levels in the serum or plasma of patients with diverse neurological diseases. Clinical studies have demonstrated that GFAP holds promise both as a diagnostic and prognostic biomarker, including but not limited to individuals with Alzheimer's disease. GFAP exhibits diverse forms and structures, herein referred to as its proteoform complexity, encompassing conformational dynamics, isoforms and post-translational modifications (PTMs). In this review, we explore how the proteoform complexity of GFAP influences its detection, which may affect the differential diagnostic performance of GFAP in different biological fluids and can provide valuable insights into underlying biological processes. Additionally, proteoforms are often disease-specific, and our review provides suggestions and highlights areas to focus on for the development of new assays for measuring GFAP, including isoforms, PTMs, discharge mechanisms, breakdown products, higher-order species and interacting partners. By addressing the knowledge gaps highlighted in this review, we aim to support the clinical translation and interpretation of GFAP in both CSF and blood and the development of reliable, reproducible and specific prognostic and diagnostic tests. To enhance disease pathology comprehension and optimise GFAP as a biomarker, a thorough understanding of detected proteoforms in biofluids is essential.

Advancing Protein Detection and Analysis Based on Ag/Au PHCN for Enhanced SERS Sensitivity and Specificity in Biomolecular Diagnostics.

In the realm of disease diagnostics, particularly for conditions such as proteinuria and hemoglobinuria, the quest for a method that combines accurate, label-free detection of protein compositions and their conformational changes remains a formidable challenge. In this study, we introduce an innovative Ag/Au plasmonic hybrid coupling nanoarray (Ag/Au PHCN) architecture marked by sub-10 nm interparticle gaps. These nanoarrays, leveraging plasmonic hybrid coupling and synergistic enhancement mechanisms, create a plethora of uniform surface-enhanced Raman spectroscopy (SERS) hotspots. The Ag/Au PHCN substrates demonstrated unparalleled sensitivity in the unmarked detection of hemoglobin (HGB), bovine serum albumin (BSA), and cytochrome C (Cyt.C) in bodily fluids, incorporating the advantages of high sensitivity, high reproducibility, durability, recyclability, and biocompatibility. Notably, the detection limits for BSA and HGB are unprecedented at 0.5 and 5 ng/mL, respectively. This achievement sets a new benchmark for label-free protein detection using two-dimensional nanostructures. Crucially, the Ag/Au PHCNs possess the novel capability to discern protein conformational changes post denaturation, underscoring their potential in probing protein functionalities. Most importantly, these nanoarrays can differentiate between normal and proteinuria-affected urine samples and monitor protein content variations over time, heralding a new era in clinical diagnostics with particular relevance to proteinuria and hemoglobinuria detection.

Postmortem distribution of ropivacaine and its metabolite in human body fluids and solid tissues by GC-MS/MS using standard addition method.

An analytical method was developed for determining ropivacaine and its main metabolite, 3-hydroxyropivacaine in biomedical samples using gas chromatography-tandem mass spectrometry (GC-MS/MS). Then, this established method was applied to investigate the distribution of ropivacaine and its metabolite in human fluids and solid tissues obtained from an authentic case ropivacaine involved. The fluid sample was added acetonitrile, and solid tissue was homogenized using a freezer mill and then added into acetonitrile. Then, an internal standard solution was added to the mixtures. The mixture was centrifuged at 12,000 × g for 5min, and the upper layer of acetonitrile was transferred to magnesium sulfate and octadecyl silica (C18) gel for cleaning up the sample. After centrifugation, the upper layer was then evaporated to dryness with nitrogen, and dissolved with methanol, then injected into the GC-MS/MS system. The coefficients of determination (r2) of constructed calibration curves were all greater than 0.999. The limits of detection for ropivacaine and 3-hydroxyropivacaine in target samples were 15ng/mL and 10ng/mL, respectively. The recovery rates of ropivacaine and 3-hydroxyropivacaine ranged from 97.6% to 103% and from 96.5% to 104%, respectively. The inter-day precision values of ropivacaine and 3-hydroxyropivacaine were not greater than 6.25% and 7.98%, respectively, and the inter-day trueness values were not greater than 6.90% and 8.33%, respectively; the intra-day precision and trueness values of ropivacaine and 3-hydroxyropivacaine were not greater than 3.20%, 6.78%, 7.84% and 8.99%, respectively. GC-MS/MS method for simultaneous detection and quantification of ropivacaine and 3-hydroxyropivacaine in biological samples was successfully developed. The method could also be applied to samples obtained from an authentic case; their distribution among tested fluids and solid tissues were also measured. This is the first report on the distribution of ropivacaine and its major metabolite 3-hydroxyropivacaine in a human case.

Serum-derived Protein Coronas Affect Nanoparticle Interactions with Brain Cells.

Neuronanomedicine is an emerging field bridging the gap between neuromedicine and nanoparticle-based drug delivery systems. Despite promise, clinical translation of neuronanomedicines remains elusive, possibly due to a dearth of information regarding the effect of the protein corona on these neuronanomedicines. The protein corona, a layer of proteins adsorbed to nanoparticles following exposure to biological fluids, ultimately determines the fate of nanoparticles in biological systems, dictating nanoparticle-cell interactions. To date, few studies have investigated the effect of the protein corona on interactions with brain-derived cells, an important consideration for the development of neuronanomedicines. Here, two polymeric nanoparticles, PLGA and PLGA-PEG, were used to obtain serum-derived protein coronas. Protein corona characterization and LC-MS analysis revealed distinct differences in biophysical properties and protein composition. PLGA protein coronas contained high abundance of globins (60%) and apolipoproteins (21%), while PLGA-PEG protein coronas contained fewer globins (42%) and high abundance of protease inhibitors (28%). Corona coated PLGA nanoparticles were readily internalized into microglia and neuronal cells, but not into astrocytes. Internalization of nanoparticles was associated with pro-inflammatory cytokine release and decreased neuronal cell viability, however, viability was rescued in cells treated with corona coated nanoparticles. These results showcase the importance of the protein corona in mediating nanoparticle-cell interactions.&#xD.

Analysis of miRNAs in milk of four livestock species

BackgroundMilk is essential for mammalian nutrition because it provides vital nutrients for growth and development. Milk composition, which is influenced by genetic and environmental factors, supports lactation, a complex process crucial for milk production and quality. Recent research has focused on noncoding RNAs, particularly microRNAs (miRNAs), which are present in body fluids and regulate gene expression post-transcriptionally. This study comprehensively characterizes miRNAs in milk of four livestock species, namely Bubalus bubalis, Capra hircus, Equus asinus, and Ovis aries and identifies potential target genes.ResultsHigh-throughput sequencing of milk RNA resulted in distinct read counts across species: B. bubalis (8,790,441 reads), C. hircus (12,976,275 reads), E. asinus (9,385,067 reads), and O. aries (7,295,297 reads). E. asinus had the highest RNA mapping rate (94.6%) and O. aries the lowest (84.8%). A substantially greater proportion of miRNAs over other small RNAs was observed for the donkey milk sample (7.74%) compared to buffalo (0.87%), goat (1.57%), and sheep (1.12%). Shared miRNAs, which included miR-200a, miR-200b, miR-200c, and miR-23a among others, showed varying expression levels across species, confirmed by qPCR analysis. Functional annotation of predicted miRNA target genes highlighted diverse roles, with an enrichment in functions linked to metabolism and immunity. Pathway analysis identified immune response pathways as significant, with several miRNAs targeting specific genes across species, suggesting their regulatory function in milk.ConclusionsBoth conserved and species-specific miRNAs were detected in milk of the investigated species. The identified target genes of these miRNAs have important roles in neonatal development, adaptation, growth, and immune response. Furthermore, they influence milk and meat production traits in livestock.

225 Kidney function and nitrogen excretion in Brown Swiss and Holstein dairy cows

Abstract The agricultural sector contributes to nitrogen (N) emissions since farm animals excrete considerable N amounts via feces and urine. To reduce N emissions by dairy cattle, methods predicting accurately individual N emissions are of great interest. Recent data showed that Brown Swiss (BS) cows have greater urea concentrations in milk and blood than Holstein (HO) cows. However, it is still unknown if greater BUN concentrations in a particular breed are congruently reflected by concomitantly increased contents of nitrogenous compounds in other media (e.g., urine and saliva). Thus, the present study simultaneously assessed biomarkers for kidney function like urea, and creatinine and symmetric dimethylarginine (SDMA) concentrations in several body fluids (i.e., blood, urine, milk, and saliva) as well as nitrogen excretion in feces in BS and HO cows under identical feeding conditions. Blood, saliva, urine, and feces were sampled in 31 multiparous BS and 46 HO cows kept under identical feeding and management conditions. Samples were collected at different lactational stages after the monthly DHIA control test-day. Concentrations of urea and creatinine were measured in serum, urine, and saliva. Symmetric dimethylarginine was determined in serum, which is an established indicator for glomerular filtration rate (GFR). Feces were analyzed for dry matter content and nitrogen concentrations. Data on milk urea and protein concentrations, and daily milk yield were obtained from the monthly DHIA test-day records. The effects of breed, time, and parity number on blood, saliva, urine, feces, and milk parameters were evaluated with the GLM procedure with breed, time, and parity number as fixed effects. Differences between BS and HO were assessed by the Tukey-corrected t-test at P < 0.05. Dry matter intake and body weight were similar in BS and HO cows (P > 0.05). No differences between BS and HO were observed for milk yield, fecal DM and nitrogen content. BS cows showed greater urea concentration (25.8 ± 0.7 vs 21.8 ± 0.7 mg/dL), and protein content in milk (3.70 ± 0.08 vs 3.45 ± 0.07%) than HO cows (P < 0.01). Concentrations of urea, creatinine, and SDMA in serum, were greater in BS than in HO cows (P < 0.01) with 5.46 ± 0.19 vs 4.72 ± 0.13 mmol/L for urea, 105.96 ± 2.23 vs 93.07 ± 1.50 mmol/l creatinine, and 16.78 ± 0.69 vs 13.39 ± 0.44 µg/dL SDMA, respectively. Urea and creatinine concentrations in urine and saliva did not differ among breeds. Despite greater urea and creatinine concentrations in blood, and milk urea content in BS compared with HO, excretion of these parameters did not differ between breeds in urine. Our results suggest a reduced renal glomerular filtration rate in BS compared with HO. The underlying mechanisms require further investigations.

Potential of Exosomes as Multifunctional Nanocarriers for Targeted Drug Delivery.

Exosomes are small vesicles that form when multivesicular bodies fuse with the plasma membrane and are released into body fluids. They play a vital role in facilitating communication between cells by transferring different biomolecules, including DNA, RNA, proteins, and lipids, over both short and long distances. They also function as vital mediators in both states of health and disease, exerting an impact on several physiological processes. Exosomes have been modified to overcome the limitations of natural exosomes to enhance their potential as carriers for drug delivery systems, and these modifications aim to improve the drug delivery efficiency, enhance tissue and organ targeting, and prolong the circulating half-life of exosomes. This review discussed recent advancements in exosome nanotechnology, as well as the progression and use of exosomes for drug delivery. The potential commercialisation and challenges associated with the use of exosome-based drug delivery systems were also discussed, aiming to motivate the development of exosome-based theranostic nanoplatforms and nanotechnology for improved healthcare treatments.

Knowledge, attitudes and beliefs regarding HIV among medical students in Zagreb, Croatia

BackgroundMedical students, as future health-care providers (HCPs) play a significant role in shaping attitudes towards people living with HIV/AIDS (PLWHA) and should possess adequate knowledge of this infection. The study aim was to assess knowledge about HIV among medical students of the University of Zagreb School of Medicine, and to determine the level of discriminatory attitudes towards PLWHA.MethodsWe assessed knowledge about epidemiology, treatment, and prevention of HIV by using closed-ended and multiple-choice questions. Likert-scale questions were employed to determine attitudes towards PLWHA. Bivariate and multivariate ordinal logistic regression was used to assess correlates of certain discriminatory attitudes.Results561 medical students participated, with 46.7% attending preclinical courses. Overall, 42.1% of students think they received sufficient information on HIV/AIDS during elementary and high school education. Among clinical students, 42.6%, 20.8% and 11.8% estimated accurately transmission risk after a needle injury, unprotected vaginal, and anal intercourse, respectively. 66.8% of clinical students were aware that treatment can prevent AIDS, while 58.7% and 69.8% were familiar with the rationale of using pre-exposure (PrEP) and post-exposure prophylaxis (PEP). In the multivariate analysis, individuals lacking infectology course attendance (aOR = 1.45; CI: 1.00–2.09) and those unaware of transmission routes (aOR = 1.49; CI: 1.06–2.09) showed higher odds of advocating HIV status disclosure compared to those who did not yet attend an infectology course. Students supporting extra protection for handling PLWHA bodily fluids were more likely to support refusal to treat PLWHA (aOR = 1.80; CI: 1.22–2.69) compared to those who did not support that opinion. Males were more inclined to state that they would refuse to treat PLWHA (aOR = 1.66; CI: 1.11–2.50) and disclose their HIV status (aOR = 1.62; CI: 1.17–2.27) than females. Overestimating needle injury transmission risk raised treatment refusal likelihood (aOR = 2.22; CI = 1.29–3.92) compared to those accurately informed of this risk.ConclusionResults indicate lack of knowledge of HIV transmission risks after specific exposures and about PrEP, PEP and treatment effectiveness. Gender and knowledge about HIV transmission risks influence students’ attitudes towards PLWHA. Medical education should be focused on fostering correct attitudes and addressing stigma, which undermines prevention and treatment outcomes of PLWHA.

Optimizing workflow efficiency for analyzing low molecular weight endogenous peptides in colostrum.

Bovine milk and colostrum play pivotal roles in the nutritional support of both human and bovine infants. Colostrum, the initial milk secretion, is crucial for neonatal growth, providing essential nutrients, growth factors, immunity, and defense mechanisms through a diverse array of bioactive compounds, including bioactive proteins and peptides. Peptidomics, leveraging the potential health benefits of peptides derived from food and body fluids, has become prominent in contemporary research. Endogenous peptides (EPs) have gained notable scientific and commercial interest due to their potential biofunctional significance in areas such as immune health, antimicrobial, anti-inflammatory, antihypertensive, and antioxidative studies. In this investigation, we aimed to extract and analyze low molecular weight EPs from colostrum using four distinct peptide extraction methods, previously employed for EPs extraction from other bodily fluids. The efficiency of these methods was systematically compared and analysed to identify the most effective extraction technique for maximizing the identification of low molecular weight EPs from colostrum. This study represents a pioneering effort as no prior research has systematically compared different extraction methods for low molecular weight EPs from colostrum. Given the unique physical and chemical composition of colostrum compared to milk and other body fluids, a comprehensive analysis of EPs extraction methods was deemed essential. In the present study, we successfully extracted over 3200 EPs from colostrum using trichloroacetic acid (TCA) and a molecular weight cut off (MWCO) extraction method. The findings of this study revealed the extraction of EPs from colostrum, demonstrating potential inherent bioactivities as predicted by in silico tools.

Ultra-Microporous Fe-MOF with Prolonged NO Delivery in Biological Media for Therapeutic Application.

Nitric oxide (NO), a key element in the regulation of essential biological mechanisms, presents huge potential as therapeutic agent in the treatment and prevention of chronic diseases. Metal-organic frameworks (MOFs) with open metal sites are promising carriers for NO therapies but delivering it over an extended period in biological media remains a great challenge due to i) a fast degradation of the material in body fluids and/or ii) a rapid replacement of NO by water molecules onto the Lewis acid sites. Here, a new ultra-narrow pores Fe bisphosphonate MOF, denoted MIP-210(Fe) or Fe(H2O)(Hmbpa) (H4mbpa = p-xylenediphosphonic acid) is described that adsorbs NO due to an unprecedented sorption mechanism: coordination of NO through the Fe(III) sites is unusually preferred, replacing bound water, and creating a stable interaction with the free H2O and P-OH groups delimiting the ultra-narrow pores. This, associated with the high chemical stability of the MOF in body fluids, enables an unprecedented slow replacement of NO by water molecules in biological media, achieving an extraordinarily extended NO delivery time over at least 70h, exceeding by far the NO kinetics release reported with others porous materials, paving the way for the development of safe and successful gas therapies.

Effect of MHD and radiation on biviscous Bingham fluid flow on Marangoni boundary for heat source/sink with chemical reaction

A significance of Marangoni-driven convective magnetohydrodynamics (MHD) was investigated in a planned study. The present study examines the impact of radiation and chemical reactions on the two dimensional boundary layer flow of bi-viscous Bingham fluid on a thermosolutal Marangoni boundary with magnetic field and heat source/sink. The physical flow problem is mathematically modelled into Navier–Stokes equations. These nonlinear partial differential equations are then mapped into a set of nonlinear ordinary differential equations using similarity transformation. The elegant analytical method is used to obtain analytic approximations for the resulting system of nonlinear differential equations. The analytical solution for the temperature and concentration profiles is expressed in terms of Kummer's confluent hypergeometric function. The features of flow characteristics such as velocity, temperature, and concentration profiles in response to the variations of the emerging parameters are simulated and examined with a physical explanation through graphs. Surface tension is considered to be corresponding to heat and mass. The results reveal that the velocity profile decreases with increasing the magnetic field, while the Marangoni number value increases with increasing the velocity profile. Moreover, the temperature profile rises with rising the radiation parameter and whereas the value chemical reaction parameter upsurges with decline concentration profile. The present problem has great interest due to its applications in industrial applications such as drying of silicon wafers, thin layers of paint, glues, in heat exchangers, crystal growth in space, biological fluids, blood, synovial liquids, plasma, lubricants, many pharmaceutical products, proteins, sewage sludge, china clay, and many more.

Platinum-perovskite nanocomposite-based Exosensor for specific detection of prostate cancer in clinical settings.

Exosomes, extracellular vesicles (EVs) with an average size of 50-150nm, transfer various biomolecules and exchange signaling molecules between cells in a paracrine manner. Molecular investigations have revealed that EVs can reflect real-time metabolic changes in normal- and cancer-origin cells and thus harbor valid diagnostic biomarkers. Despite these advantages, the detection of low concentrations of cancer cell EVs in biological fluids is still a great challenge. Here, a new electrochemical Exosensor based on platinum-perovskite is developed for the direct detection of EVs using a biotinylated monoclonal CD63 antibody as a capture element. The label-free method exhibited higher sensitivity with a lower limit of quantification of 2000 EVs/µL with a dynamic linear range (LDR) of 2000 to 14,000 EVs/μL compared with other available methods. To enhance the selectivity of detection, EVs were simultaneously sandwiched between secondary antibodies of PSA (prostate-specific antigen), as an FDA-approved prostate cancer biomarker. Data indicated that this Exosensor can distinguish normal and cancer EVs in samples from healthy individuals and prostate cancer patients. Taken together, this technology offers a unique approach to label-free quantification of EVs and cancer detection in the early stages.

Melt-blown polypropylene nonwoven as an efficient and eco-economic sorbent for pipette tip micro-solid phase extraction for the determination of tyrosine kinase inhibitors

BackgroundThe detection of tyrosine kinase inhibitors (TKIs) in biological fluids is essential due to their critical role in cancer therapy and the variability in individual drug metabolism, which necessitates precise dosing. Traditional methods for analyzing TKIs in biological fluids, such as blood plasma, typically involve complex sample preparation techniques that can be resource-intensive, environmentally burdensome, and not sufficiently sensitive for low-concentration analytes. There is a pressing need for more efficient, economical, and environmentally friendly methods that can enhance sensitivity and throughput without compromising accuracy. ResultsThis study explores the use of melt-blown polypropylene nonwoven (MBPP), commonly found in face masks, as a novel sorbent for pipette-tip micro-solid phase extraction (PT-μSPE). MBPP demonstrated excellent hydrophobicity and significant mesoporous adsorption capacity. An extraction device was fashioned by inserting a segment of MBPP (15 mg) into a 200 μL disposable plastic pipette tip, which was then attached to a 2.5 mL disposable plastic syringe. The MBPP's fabric form removes the need for a frit, allowing the extraction process to be completed in just 3 min through simple plunger manipulation. The method achieved extraction recoveries ranging from 60.5% to nearly 100%. Subsequent method validation using liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed satisfactory linearity (coefficient of determination R2 > 0.993), accuracy (relative recoveries: 86.3%–114.8%), and precision (relative standard deviation: 3.4%–11.3%), with detection limits between 0.022 and 0.135 ng mL-1. SignificanceThe introduction of MBPP for PT-μSPE represents a significant advancement in the bioanalytical detection of TKIs, offering a highly efficient, cost-effective, and environmentally sustainable method. It compares favorably with existing techniques, offering advantages in terms of cost, environmental impact, and ease of use. This approach has the potential to be widely adopted for routine monitoring of TKIs in clinical settings.

Post-mortem utility of Neuron Specific Enolase (NSE) and Calcium Binding Protein B (S100B) for differentiating traumatic brain injury from other causes of death.

In forensic pathology, identifying causes of death in traumatic brain injuries (TBIs) devoid of observable signs presents a significant challenge. Post-mortem biochemistry plays a crucial role in forensic medicine, particularly in determining causes of death in TBIs that lack macroscopic or histopathological evidence. This study aimed to evaluate the utility of Neuron Specific Enolase (NSE) and S100 Calcium Binding Protein B (S100B) in post-mortem serum and cerebrospinal fluid (CSF) as markers for TBI. The relationship of these biochemical markers with survival time and post-mortem interval was also studied. The study sample consisted of 63 cases each from the TBI and the Non-TBI (NTBI) group. The NTBI group comprised of deaths due to mechanical asphyxia, myocardial infarction and isolated trunk trauma. While serum S100B and CSF NSE emerged as a promising marker for TBI, CSF S100B failed to differentiate TBI from the other causes of death. The absence of an association between the level of markers and survival time or post-mortem interval in TBIs highlights the limitations of these biomarkers in such contexts. This study underscores the potential of biochemical markers like serum S100B and CSF NSE in identifying TBI deaths, aiding forensic diagnoses where there are evidentiary limitations in traditional methods. Further research exploring additional markers and body fluids could enhance diagnostic precision in forensic neuropathology.