Level Of Fragmentation Research Articles

Gene Expression, Oxidative Stress, and Neurotransmitters in Rotenone-induced Parkinson’s Disease in Rats: Role of Naringin from Citrus aurantium via Blocking Adenosine A2A Receptor

Background:: Lack of control in voluntary movements, resting tremor, postural instability, and stiffness are the hallmarks of Parkinson's disease (PD). Objective:: The current work's objective is to assess naringin isolated from Citrus aurantium L. peels as an anti-parkinsonism agent in rats. Methods:: The HPLC and LC-ESI-MS analysis of Citrus aurantium L. peels methanol extract was done. The behavioral, biochemical, genetic, and histopathological analysis were evaluated in parkinsonism rats. Results:: Fourteen phenolics and nine flavonoids were found in the extract, according to the HPLC analysis, while LC-ESI-MS analysis revealed the presence of twenty-six flavonoids. The dominant flavonoid subclasses were 4 aglycones, 11 monoglycosides, 5 diglycosides, and 6 polymethoxy flavonoids, beside 4 coumarines, 4 alkaloids and a limonin triterpene. Adenosine A2A receptor (A2AR) gene expression, malondialdehyde (MDA), interleukin-6 (IL-6), caspase-3 (Cas-3) and DNA fragmentation levels significantly increased in rotenone-treated rats. Dopamine (DA), norepinephrine (NE), serotonin (5-HT), reduced glutathione (GSH), succinate, and lactate dehydrogenase (SDH &LDH) levels all significantly decreased. Treatment with naringin and A2AR antagonists enhanced the animals’ behavior and improved all the selected parameters. The brain hippocampal features confirmed our results. Conclusion:: Naringin could be considered a nutraceutical agent by attenuating the neurodegeneration associated with PD via blocking adenosine A2AR.

Elucidating the impact of Y chromosome microdeletions and altered gene expression on male fertility in assisted reproduction.

Genetic abnormalities like Y chromosome microdeletions are implicated in male infertility. This study investigated the association of azoospermia factor (AZF) region microdeletions with unsuccessful assisted reproductive techniques (ART), including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). This cross-sectional analysis study examined 80 Iranian oligospermic men (mean age 34years) with prior failed ICSI and IVF cycles (IR.IAU.TNB.REC.1401.041). Semen analysis evaluated quantity/quality parameters based on World Health Organization guidelines. Participants were stratified by sperm DNA fragmentation (SDF) levels into: control (SDF < 15%, n = 20), mild elevation (15% ≤ SDF ≤ 30%, n = 60), and high (SDF > 30%, n = 20). Multiplex PCR mapped AZF microdeletions in the high SDF group. The AZF-associated genes were selected by RNA Seq analysis, and the candidate genes were checked for expression level by real-time PCR. High SDF individuals exhibited poorer semen metrics, including 69% lower sperm concentration (P = 0.04) than those without SDF. Of this subset, 45% (9/20 men) harboured predominately AZF microdeletions. Men with AZF microdeletions showed higher SDF (32% vs 21%, P = 0.02) and altered AZF-associated genes expression. As USP9Y 3-fold, UTY 1.3-fold, and BPY2 1-fold revealed up-regulation, while IQCF1 8-fold, CDY 6.5-fold, DAZ 6-fold, and DDX3Y 1-fold underwent down-regulation. The PAWP gene was also down-regulated (5.7-fold, P = 0.029) in the IVF/ICSI failure group. AZF microdeletions significantly impact male infertility and ART outcomes. High SDF individuals exhibited poorer semen metrics, with 45% AZF microdeletions. These microdeletions altered AZF-associated genes expression, affecting fertility mediator PAWP independently. Dual AZF and SDF screening enables personalized management in severe male infertility, potentially explaining IVF/ICSI failures.

#1683 Gut permeability, circulating bacterial fragments, and left ventricular strain in peritoneal dialysis

Abstract Background and Aims There are limited data on the association of gut permeability, circulating bacterial fragment load, left ventricular strain in patients on peritoneal dialysis (PD). We aimed to measure circulating bacterial fragments, NT-proBNP, calprotectin and zonulin levels, and to evaluate their association with gut permeability, circulating bacterial fragment load, left ventricular strain and clinical outcomes on PD patients. Method We performed a single-center prospective cohort study. Patients who were planned for peritoneal dialysis were recruited. Serum endotoxin, bacterial DNA, NT-proBNP, calprotectin and zonulin levels were measured. Primary outcomes were technical and patient survival, secondary outcomes were hospitalization data. Results One hundred and eight patients were recruited. No correlations between circulating bacterial fragments, NT-proBNP, calprotectin and zonulin levels in PD patients. Circulating bacterial fragments, calprotectin and zonulin levels are positively correlated with insulin resistance index (bacterial DNA: P = .002, calprotectin: P = .014, zonulin: P = .006), while NT-proBNP level is associated with volume overload in PD patients (volume of overhydration: P = .000, E:I ratio: P = .000), peritoneal characteristics (D/P4: P = .004, MTAC: P = .048). NT-proBNP level have a negative correlation with nutritional characteristics (albumin: P = .000, hemoglobin: P = .033) and residual GFR (P = .000). In univariate analysis of PD patient survival, NT-proBNP is associated with patient survival (P = .003), but this association become insignificant after multivariate analysis of clinical confounding factors. NT-proBNP is the strongest independent predictor of technical survival rate in PD patients (P = .005). Patients in the highest tertiles of NT-proBNP and calprotectin have lower technical survival rates, but only patients in the highest tertiles of NT-proBNP, not calprotectin, have lower patient survival. NT-proBNP is also correlated with the number of hospitalizations per year (P = .004) and total hospitalization time (P = .012) in PD patients. Endotoxin and bacterial DNA levels in PD patients have no predictive value for PD patient survival, technical survival, number of hospitalizations per year, and total hospitalization time. Conclusion There is no correlation between gut permeability, circulating bacterial fragments, and impairment of left ventricular function in PD patients. Circulating bacterial fragments levels and gut permeability are associated with insulin resistance, while impairment of left ventricular function is associated with solution overload. Bacterial fragment levels have no predictive value on survival rate, technical survival rate and hospitalizations data in PD patients. NT-proBNP is the strongest independent predictor of technical survival rate in PD patients.

Extension of reliability information of Z-numbers and fuzzy cognitive map: Development of causality-weighted rock engineering system to predict and risk assessment of blast-induced rock size distribution

Blasting operations in surface mines have the primary purpose of fragmenting the rock mass into a size that is optimal and economically viable for the mine. This ideal size has an impact on every step of the mining operation, from loading and hauling through crushing and grinding. To put it another way, the economics of the mine or facility as a whole are significantly impacted by having the ideal size distribution. This research offers a causality-based rock engineering system (RES) for risk assessment and prediction of rock fragmentation generated by blasting in surface mines. The fuzzy cognitive map was utilized in the proposed approach in order to weight the RES in accordance with the reliability information provided by the Z-number theory. This model of the RES that is weighted according to causality and based on reliability is abbreviated as causality-weighted rock engineering system based on reliability (CWRESR). The construction of the model makes use of a database that was obtained from the Sarcheshmeh copper mine. The findings indicated that the overall risk level of fragmentation was somewhere between high and very high, with a vulnerability index (VI) of 69.73 cm. As a result, controlled blasting operations are strongly advised as a means of lowering the amount of risk. In addition, the suggested model was able to predict rock fragmentation with a coefficient of determination (R2) of 0.9462 and 9646 for the training and testing phase, respectively, demonstrating that the CWRESR model is superior to other models in its ability to predict rock fragmentation.

Genotyping of rams based on melatonin receptor 1A gene polymorphisms: a tool in sire selection?

Context Several polymorphisms in the melatonin receptor 1A gene (MTNR1A ) have been related to reproductive performance in ovine. Aims To investigate the effect of the Rsa I and Mnl I polymorphisms on ram seminal quality. Methods Eighteen Rasa Aragonesa rams were genotyped for the Rsa I (C/C, C/T, T/T) and Mnl I (G/G, G/A, A/A) allelic variants of the MTNR1A gene. Individual ejaculates were analysed once a month throughout the whole year. Sperm motility, morphology, membrane integrity, levels of reactive oxygen species (ROS), phosphatidylserine (PS) inversion, DNA fragmentation and capacitation status were assessed. The effect of the season and polymorphisms on seminal quality was evaluated by mixed ANOVA. Key results Both polymorphisms had an effect on membrane integrity and viable spermatozoa with low levels of ROS and without PS translocation, and Rsa I also on motile and DNA-intact spermatozoa. An interaction between both polymorphisms was found, pointing to a negative effect on seminal quality of carrying the T or A allele in homozygosity. Differences were higher in the reproductive than in the non-reproductive season. Conclusions Mutations substituting C by T and G by A at Rsa I and Mnl I polymorphic sites, respectively, in the MTNR1A gene in rams could decrease the seminal quality. Implications Genotyping of rams based on melatonin receptor 1A could be a powerful tool in sire selection.

Quantifying the contribution of lignin to humic acid structures during composting

The transformation behavior of different types of lignin structure was investigated during composing with particular interest of revealing the contribution rate of lignin functional groups as well as their interaction to humic acids (HA). Rice straws, tree branches, and pine needles were selected as composting materials, because they predominantly contain G-S-H, G-S, and G-type lignin. Results showed that microorganisms were the driving force behind the conversion of lignin into HA. During composting, appeared different levels of cleavage, tearing, and fragmentation on the superficial lignin structures. In depth analysis of lignin transformation, lignin primarily consisted of aromatic groups, CO bonds, alkyl groups, hydroxyl groups and linkage between monomeric units (β-O-4, β-5 and β-β) in the early stage of composting. As lignin degraded, the CO bonds were gradually exposed. But due to their unstable nature, the CO bonds were prone to undergo changes with the cleavage of the aromatic rings at positions 2, 5, and 6 during composting. CO bonds could be converted into aromatic rings, alkyl groups, hydroxyl groups, and CO groups in HA. Through multiple linear regression analysis, it could be concluded that the CO bonds in G-type and S-type monomeric units contributed significantly to the aromatic rings, accounting for 30.4 % and 48.4 %, respectively. The main mechanism might be related to the cleavage of CO bonds and subsequent atomic rearrangement after the release of carbon atoms. This in-depth analysis filled the gap in the mechanism of HA formation during composting.

In-Electrospray source Hydrogen/Deuterium exchange coupled to multistage fragmentation for the investigation of the protonation and fragmentation pathways of gas phase ions.

Identification of molecules in complex natural matrices relies on matching the fragmentation spectra of ions under investigation and the spectra acquired for the corresponding analytical standards. Currently, there are many databases of experimentally measured tandem mass spectrometry spectra (such as NIST, MzCloud, and Metlin), and considerable progress has been made in the development of software for predicting tandem mass spectrometry fragments in silico using combinatorial, machine learning, and quantum chemistry approaches (such as MetFrag, CFM-ID, and QCxMS). However, the electrospray ionization molecules can be ionized at different sites (protonated or deprotonated), and the fragmentation spectra of such ions are different. Here, we are using the combination of the in-ESI source hydrogen/deuterium exchange reaction and MSn fragmentation for the investigation of the fragmentation pathways for different protomers of organic molecules. It is shown that the distribution of the deuterium in the fragment ions reflects the presence of different protomers. For several molecules, the distribution of deuterium was traced up to the MS5 level of fragmentation revealing many unusual and unexpected effects. For example, we investigated the loss of HF from the ciprofloxacin and norfloxacin ions and observed that for ions protonated at -COOH group, the eliminating hydrogen always comes from -NH group. When ions are protonated at another site, the elimination of hydrogen with a probability of 30% occurs from the -NH group, and with a probability of 70%, it originates from other sites on the molecule. Such effects were not described previously. Quantum chemical simulation was used for the verification of the protonated structures and simulation of the corresponding fragmentation spectra.

Protective Effects of Cannabidiol (CBD) against Qxidative Stress, but Not Excitotoxic-Related Neuronal Cell Damage-An In Vitro Study.

Cannabidiol (CBD) appears to possess some neuroprotective properties, but experimental data are still inconsistent. Therefore, this in vitro study aimed to compare the effects of CBD in a wide range of concentrations on oxidative stress and excitotoxic-related cell damage. Results showed that low concentrations of CBD ameliorated the H2O2-evoked cell damage of primary cortical neuronal cell culture. However, higher concentrations of CBD alone (5-25 μM) decreased the viability of cortical neurons in a concentration-dependent manner and aggravated the toxic effects of hydrogen peroxide (H2O2). Neuroprotection mediated by CBD in primary neurons against H2O2 was not associated with a direct influence on ROS production nor inhibition of caspase-3, but we found protective effects of CBD at the level of mitochondrial membrane potential and DNA fragmentation. However, CBD had no protective effect on the glutamate-induced cell damage of cortical neurons, and in higher concentrations, it enhanced the toxic effects of this cell-damaging factor. Likewise, CBD, depending on its concentration, at least did not affect or even enhance cortical cellular damage exposed to oxygen-glucose deprivation (OGD). Finally, we showed that CBD in submicromolar or low micromolar concentrations significantly protected human neuronal-like SH-SY5Y cells against H2O2- and 6-hydroxydopamine (6-OHDA)-induced cell damage. Our data indicate that CBD has a dual effect on oxidative stress-induced neuronal death-in low concentrations, it is neuroprotective, but in higher ones, it may display neurotoxic activity. On the other hand, in excitotoxic-related models, CBD was ineffective or enhanced cell damage. Our data support the notion that the neuroprotective effects of CBD strongly depend on its concentration and experimental model of neuronal death.

D-dimer- a multifaceted molecule.

D-dimer, a universally unique marker for fibrin degradation, is generated through the enzymatic interplay of thrombin, factor XIIIa, and plasmin. The emergence of D-dimer-containing fibrin molecules occurs in both intravascular and extravascular spaces during pivotal physiological processes like haemostasis, thrombosis, and tissue repair. Given the inherently physiological nature of fibrin formation and fibrinolysis, basal levels of D-dimer fragments are present in plasma. Beyond its role as a marker of routine physiological processes, aberrations in D-dimer levels are indicative of a spectrum of conditions, both non-pathological and pathological. The clinical utility of D-dimer has been firmly established, particularly in scenarios like venous thromboembolism (VTE), pulmonary embolism (PE), deep vein thrombosis (DVT), and disseminated intravascular coagulation (DIC). Additionally, recent applications have extended to assess the prognosis of COVID-19. While D-dimer is commonly associated with thrombotic conditions, its elevation is not confined to these conditions alone. Elevated D-dimer levels are observed across various diseases, where its significance extends beyond diagnostic indicators to prognostic implications.

Labilization of the DNA structure in peripheral blood lymphocytes of COVID-19 patients

Introduction. Available data indicate the SARS-CoV-2 coronavirus to be potent of impairing DNA repair processes and cause oxidative stress, which can lead to the accumulation of DNA damage in human cells. However, the DNA-damaging effect of the virus has not yet been sufficiently studied. The purpose of the research was to study the ability of SARS-CoV-2 to cause DNA damage in human peripheral blood lymphocytes. Materials and methods. One hundred forty COVID-19 patients and 24 donors of the control group are included in the study. The level of DNA fragmentation in lymphocytes was determined by alkaline DNA-comet assay. Statistical differences between the mean medians of the «%DNA in the comet tail» (tail DNA%) were assessed using Student’s t-test. The Jeffers test was used to compare the proportions of cells with different levels of DNA-damage. Statistical differences between groups were assessed using the Mann-Whitney test. Results. In the COVID-19 patients, an increase in the level of breaks and alkali-labile sites in DNA was revealed when compared to controls (p = 0.025). In the group of patients infected with SARS-CoV-2, the proportion of comets with DNA damage of up to 5% decreased (p = 0.009), while the proportion of comets containing more than 10% DNA tail increased (p = 0.000). The number of atypical comets compared to the control increased by 3.7 and 5.9 times with mild and moderate severity of the disease, respectively (r = 0.993; p = 0.001). In the association with diseases – coronary heart disease (CHD) and diabetes mellitus type II (DM type 2), the level of DNA fragmentation in lymphocytes statistically significantly increased compared to the group of patients without these diseases. Limitations. A limitation is the lack of data on DNA-structure damage in severe COVID-19 disease. Conclusion. SARS-CoV-2 infection leads to labilization of the DNA structure in human peripheral blood lymphocytes. The level of DNA damage depends on the severity of COVID-19 and the presence of comorbid diseases: CHD and DM type 2. The results of the study are important for understanding the mechanisms of action of the virus on human immunocompetent cells.

Extracellular matrix turnover proteins as risk markers in people with type 2 diabetes and microalbuminuria

BackgroundThis post-hoc study investigated whether biomarkers reflecting extracellular matrix (ECM) turnover predicted cardiovascular disease (CVD), mortality, and progression of diabetic kidney disease (DKD) in individuals with type 2 diabetes (T2D) and microalbuminuria. MethodsSerum levels of specific ECM turnover biomarkers were assessed in 192 participants with T2D and microalbuminuria from an observational study conducted at Steno Diabetes Center Copenhagen from 2007 to 2008. Endpoints included CVD events, mortality, and DKD progression, defined as decline in estimated glomerular filtration rate (eGFR) of >30 %. ResultsParticipants had a mean age of 59 years, with 75 % males. Over a median follow-up of 4.9 to 6.3 years, the study recorded 38 CVD events, 24 deaths, and 40 DKD events. Elevated levels of a degradation fragment of collagen type I (C1M) were associated with an increased risk of >30 % eGFR decline, although this association was not independent of other risk factors. No significant associations were found between other ECM turnover biomarkers and DKD progression, mortality, or CVD risk. ConclusionElevated C1M levels were linked to DKD progression in individuals with T2D and microalbuminuria, but not independently of other risk factors. None of the ECM turnover biomarkers were associated with CVD or mortality.

The impact of habitat loss and fragmentation on biodiversity in global protected areas

Protected areas (PAs) serve as effective means for biodiversity conservation but face threats from habitat loss and fragmentation. Current research on the impact of habitat loss or habitat fragmentation on biodiversity in PAs mostly focuses on individual PA or regional scales. At the global scale, the extent of habitat loss and fragmentation in PAs and their effects on biodiversity remains unclear. Therefore, we investigated the degree of habitat loss and fragmentation in global PAs from 2000 to 2020, analyzed the impact of habitat loss and fragmentation on biodiversity in PAs, identified hotspot PAs of severe habitat loss or fragmentation, and highlighted critically endangered species within these PAs. Our study reveals that, between 2000 and 2020, 19 % of global PAs experienced habitat loss, and 34 % experienced habitat fragmentation, with large PAs and South American tropical PAs exhibiting the most severe levels of habitat loss and fragmentation. The impact of habitat loss and fragmentation on biodiversity was most significant in small PAs and African tropical PAs. There are 10 global hotspot PAs of habitat loss or fragmentation, posing a serious threat to the survival of endangered species within PAs. Biodiversity conservation remains a prominent research focus globally, and the issues of habitat loss and fragmentation in PAs may impact the achievement of the COP15 biodiversity conservation goals. Therefore, this study aims to provide data support and scientific guidance for the management and development of global PAs.

From past habitats to present threats: tracing North American weasel distributions through a century of climate and land use change

ContextShifts in climate and land use have dramatically reshaped ecosystems, impacting the distribution and status of wildlife populations. For many species, data gaps limit inference regarding population trends and links to environmental change. This deficiency hinders our ability to enact meaningful conservation measures to protect at risk species.ObjectivesWe investigated historical drivers of environmental niche change for three North American weasel species (American ermine, least weasel, and long-tailed weasel) to understand their response to environmental change.MethodsUsing species occurrence records and corresponding environmental data, we developed species-specific environmental niche models for the contiguous United States (1938–2021). We generated annual hindcasted predictions of the species’ environmental niche, assessing changes in distribution, area, and fragmentation in response to environmental change.ResultsWe identified a 54% decline in suitable habitat alongside high levels of fragmentation for least weasels and region-specific trends for American ermine and long-tailed weasels; declines in the West and increased suitability in the East. Climate and land use were important predictors of the environmental niche for all species. Changes in habitat amount and distribution reflected widespread land use changes over the past century while declines in southern and low-elevation areas are consistent with impacts from climatic change.ConclusionsOur models uncovered land use and climatic change as potential historic drivers of population change for North American weasels and provide a basis for management recommendations and targeted survey efforts. We identified potentially at-risk populations and a need for landscape-level planning to support weasel populations amid ongoing environmental changes.

Landscape metrics for land use/cover change and green space pattern in Can Tho city in 1998-2020 based on remote sensing and GIS

Changes in land cover/green space in Can Tho city in the period 1998-2020 were analyzed based on remote sensing data and the perspective of landscape ecology. The data collected from JAXA on land cover/land use classification entire Can Tho city in the period 1998-2020 was used to extract landscape metrics and to analyze the changes by a conversion matrix. The result shows a complex change in the urban green space in the period 1998 - 2020 in Can Tho. Research results show that Can Tho city had rice paddies and other croplands accounting for the majority of the land use structure. In the period 1998-2020, the city experienced a major shrinkage in croplands. Although other land use/cover types fluctuated differently, the fragmentation process still prevailed with fragments having discrete connections in space. The process of urbanization occurred with the expansion of built-up, but the concentration level was not high, with small fragments appearing sporadically distributed. However, comparing the landscape indices in the period 1998 – 2020 showed the aggregation process was increasingly taking place, and the level of fragmentation had tended to decrease. This trend was evidenced by the sharp increase in the number of patches, effective mesh size, and splitting index simultaneously with the gradual decline of the LPI index. The research results show high potential in expanding green space in Can Tho as well as application in planning urban green space development.

Impacts of habitat loss and fragmentation on seed dispersal by an Afrotropical bird community in an anthropogenic landscape: Insights from movement models

Habitat loss and fragmentation can affect seed dispersal by impacting seed dispersers' habitat choices, behavior, and movement patterns. Here we studied seed dispersal by an Afrotropical bird community in an anthropogenic landscape in Kenya. We used telemetry data of six bird species, estimated their habitat choices, behavior, and movement patterns in the forest fragments and the matrix. We then integrated our model estimates into a seed dispersal simulation model with multiple artificial anthropogenic landscapes, experiencing different levels of habitat loss and fragmentation. In our simulations, we included two seed disperser groups: forest specialist and habitat generalist birds that moved in the landscape using a mixture-correlated random walk, and encamped and traveled in the different habitat types. Increased habitat loss diminished seed dispersal distances, where seeds carried by forest specialist dispersers suffered a stronger reduction in dispersal distances compared to habitat generalists, and number of seeds deposited in habitat fragments, where fewer seeds were deposited into the fragments by habitat generalist dispersers compared to forest specialists. The effects of habitat fragmentation were similar to but weaker than that of habitat loss, and most apparent at an intermediate level of habitat loss. Other seed dispersal metrics, including spatial extent of seed rain and nearest neighbor distances among seeds, did not show any strong relationships with either habitat loss or fragmentation. Therefore, movement models offer valuable perspectives on how habitat loss and fragmentation can influence seed dispersal patterns, by reliably estimating habitat choices, behavior, and movement patterns of dispersers, and potentially benefiting efforts to conserve this ecological interaction.

Abstract 155: Plasma Kallikrein Is A Key Driver Of Basal Activation Of Coagulation Under Conditions Of C1 Inhibitor Deficiency

C1 inhibitor (C1INH) functions as a key endogenous inhibitor of contact pathway coagulation factors XII, XI and plasma kallikrein (PKa). Patients with a congenital deficiency in C1INH suffer from a rare swelling disorder called hereditary angioedema (HAE) caused by excess bradykinin generation. Patients with HAE also have elevated circulating levels of markers of activation of coagulation and an increased risk of venous thromboembolism, phenotypes recapitulated in C1INH-deficient mice. We sought to evaluate the molecular mechanism by which C1INH deficiency leads to increased basal activation of coagulation and venous thrombosis. We hypothesized that PKa serves as a key driver of activation of coagulation in humans and mice with congenital C1INH deficiency. Patients with C1INH deficiency-associated HAE were treated with the PKa inhibitor lanadelumab with plasma samples collected before and after treatment. Plasma levels of coagulation markers and contact pathway-initiated thrombin generation were determined. C1INH-deficient mice were treated with the PKa inhibitor avoralstat, the FXIIa inhibitor garadacimab, FXII small interfering RNAs, FXI antisense oligonucleotides, the anti-tissue factor antibody 1H1 or appropriate controls and plasma coagulation markers were measured. Treatment of HAE patients with the PKa inhibitor lanadelumab significantly reduced plasma levels of prothrombin fragment 1.2, thrombin antithrombin (TAT) complexes and D-dimer at 6 months after treatment initiation (P&lt;0.05). Interestingly, landalumab had no significant effect on contact pathway-initiated thrombin generation. In experiments with C1INH deficient mice, TAT complexes were significantly reduced by PKa inhibition (P&lt;0.01) but not by inhibition of FXIIa or FXIa. Interestingly, tissue factor inhibition also significantly reduced plasma TAT complexes (P&lt;0.01). This data suggests that under conditions of C1INH deficiency PKa potentiates activation of coagulation through a non-canonical pathway involving tissue factor. These findings demonstrate that C1INH is a physiologically relevant anticoagulant with C1INH deficiency resulting in enhanced kallikrein-mediated activation of basal coagulation.

A Critical Review Based on Preclinical Studies of Medicinal Plants for the Management of Alzheimer’s Disease

Abstract: Alzheimer’s disease (AD) is the most common neurodegenerative and progressive disorder that results in damage to memory and alters thinking and behavior, which represent critical problems the world’s aging population is faced with. Clinical symptoms of AD include cognitive decline, loss of memory, emotional and behavioral changes, loss of motor coordination, and mental impairments. Yet, neither a universally accepted diagnosis with respect to its pathogenesis nor an ideal therapy is available for the management of AD. The existing drugs cause many complications and adverse effects. Herbal drugs, supported by an abundance of traditional knowledge, may fulfill the need as they can target the pathogenesis of AD at various destinations, both at the cellular and molecular levels. In recent years, herbal drugs and formulations have been evaluated in preclinical setups, especially involving rat and mouse models of AD, which have shown their memoryenhancing, neuroprotective, and antioxidant activities. Several herbal drugs and phytochemicals have been evaluated for their effectiveness as antioxidative agents to prevent the occurrence of oxidative stress and ROS formation during AD pathogenesis and exhibit antiapoptotic properties by downregulating caspase-3, DNA fragmentation, NF-κB, interleukin-1 β (IL1β), and TNF levels. In this paper, we have primarily reviewed herbal remedies that have been recently evaluated as alternative treatments for AD in a preclinical setup, and discussed the role of herbal medicines in the management of AD and advances in their knowledge.

Effects of clonal fragmentation on Pyrrosia nuda depend on growth stages in a rubber plantation.

Clonal fragmentation helps to assess clonal plants' growth resilience to human and environmental disturbance. Although clonal integration in epiphytes in tropical rubber plantations is important to understand their role in enhancing biodiversity and ecosystem services, research on this subject is limited. These plantations are typically monospecific economic forests that face increased anthropogenic disturbances. In this study, we selected the clonal fern Pyrrosia nuda to study its survival status, biomass, maximum quantum yield of photosystem II (Fv/Fm), and frond length in response to the level of clonal fragmentation in a tropical rubber plantation. The results showed that (1) clonal fragmentation significantly negatively affected the survival rate, biomass, and frond length of clonal plants, but with minimal effects on Fv/Fm at different growth stages; (2) the performance of a ramet (e.g., biomass or frond length) increased with ramet developmental ages and decreased with the number of ramets in a clonal fragment. The age-dependent impacts of clonal fragmentation provide insights into the biodiversity conservation of epiphytes and forest management in man-made plantations. Therefore, to better conserve the biodiversity in tropical forests, especially in environment-friendly rubber plantations, there is a need to reduce anthropogenic disturbances and alleviate the level of fragmentation.

The risk of contact between visitors and Borrelia burgdorferi-infected ticks is associated with fine-scale landscape features in a southeastern Canadian nature park

BackgroundInfectious diseases are emerging across temperate regions of the world, and, for some, links have been made between landscapes and emergence dynamics. For tick-borne diseases, public parks may be important exposure sites for people living in urbanized areas of North America and Europe. In most cases, we know more about the ecological processes that determine the hazard posed by ticks as disease vectors than we do about how human population exposure varies in urban natural parks.MethodsIn this study, infrared counters were used to monitor visitor use of a public natural park in southern Quebec, Canada. A risk index representing the probability of encounters between humans and infected vectors was constructed. This was done by combining the intensity of visitor trail use and the density of infected nymphs obtained from field surveillance. Patterns of risk were examined using spatial cluster analysis. Digital forest data and park infrastructure data were then integrated using spatially explicit models to test whether encounter risk levels and its components vary with forest fragmentation indicators and proximity to park infrastructure.ResultsResults suggest that, even at a very fine scales, certain landscape features and infrastructure can be predictors of risk levels. Both visitors and Borrelia burgdorferi-infected ticks concentrated in areas where forest cover was dominant, so there was a positive association between forest cover and the risk index. However, there were no associations between indicators of forest fragmentation and risk levels. Some high-risk clusters contributed disproportionately to the risk distribution in the park relative to their size. There were also two high-risk periods, one in early summer coinciding with peak nymphal activity, and one in early fall when park visitation was highest.ConclusionsHere, we demonstrate the importance of integrating indicators of human behaviour visitation with tick distribution data to characterize risk patterns for tick-borne diseases in public natural areas. Indeed, understanding the environmental determinants of human-tick interactions will allow organisations to deploy more effective risk reduction interventions targeted at key locations and times, and improve the management of public health risks associated with tick-borne diseases in public spaces.

Cumulus matrix selection leads to isolation of spermatozoa with better motility, morphology, and lower DNA fragmentation.

The objective of this study was to compare the motility, morphology, and levels of DNA fragmentation of spermatozoa subjected to conventional swim-up or cumulus matrix (CM) sperm selection. Semen samples were collected from 60 normozoospermic men at a private hospital between December 2021 and March 2022. After liquefaction, semen samples were separated into two portions - one part was subjected to conventional swim-up preparation and the remaining spermatozoa were subjected to CM selection. The CM was obtained by mechanical isolation from healthy donor oocytes. Semen analysis and evaluation of sperm were performed according to WHO 6th Edition Laboratory Manual and Kruger's strict criteria, respectively. Sperm DNA fragmentation (SDF, %) of the two preparations was evaluated using Halosperm G2 detection kit (Halotech, Madrid, Spain). Wilcoxon rank-sum test was used to compare the characteristics of spermatozoa obtained by the two preparations. Spermatozoa selected by CM showed significantly better rapidly progressive motility (43.5% vs. 30.6%, respectively, p<0.001), higher percentage of morphologically normal forms (14.0% vs. 9.0%, respectively, p<0.05), and lower levels of SDF (26.0% vs. 45.0%, p<0.05) in comparison to those prepared by conventional swim-up. Moreover, the incidence of multiple sperm defects was considerably lower in the samples that underwent CM selection compared to those that did not (30.0% vs. 49.0%, respectively, p<0.05).The selection by CM significantly increases sperm motility and reduces morphologically abnormal spermatozoa and DNA fragmentation rates in comparison to the conventional swim-up preparation. The application of this selection technique may increase chances of successful IVF outcomes.