Significant Elevation Research Articles

Radiotherapy and inflammaging: the influence of prostate cancer radiotherapy on systemic inflammation

PurposeThe present study was performed to investigate the association of prostate cancer radiotherapy with inflammaging, a condition characterized by the elevation of inflammatory blood parameters that significantly increases the susceptibility to the occurrence or progression of age-related conditions.Patients and MethodsA total of 306 patients treated with curative radiotherapy (RT) for prostate cancer were enrolled into the prospective study. Aging-related inflammatory parameters including C-reactive protein (CRP), albumin, fibrinogen, cholesterol, platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were analyzed before and at the end of RT, and 3 and 15 months after completion of the RT. Statistical analysis was performed using non-parametric variance analysis.ResultsOverall variance analysis showed a significant influence of RT on all inflammatory parameters (p < 0.001) with the exception of CRP (p = 0.498). Pairwise analysis revealed a significant elevation of fibrinogen (p = 0.041), NLR (p < 0.001), and PLR levels (p < 0.001) as well as a significant decrease of albumin (p < 0.001) and cholesterol levels (p < 0.001) during the RT course. After completion of RT, a significant recovery was detected for NLR, PLR, albumin and cholesterol. However, 15 months after RT, PLR, fibrinogen, and cholesterol remained significantly lower when compared to the baseline (p < 0.001).ConclusionOur results indicate that radiation therapy triggers chronic inflammatory processes that could contribute to the development, acceleration or worsening of age-related alterations and conditions. Further investigations to estimate the long-term consequences of curative radiation therapy on clinical manifestations of aging are warranted.

The Northern Giona Fault Zone, a Major Active Structure Through Central Greece

The steep northern slopes of Giona Mt in central continental Greece are the result of an E-W normal fault dipping 35–45° to the north, extending from the Mornos River in the west to the village of Gravia in the east. This fault creates a significant elevation difference of approximately 1500 m between the northern Giona footwall and the southern Iti hanging wall. The footwall comprises imbricated Mesozoic carbonates of the Parnassos unit, which exhibit large-scale drag folding near and parallel to the fault. The hanging wall comprises deformed sedimentary rocks of the Beotian unit and tectonic klippen of the Eastern Greece unit, forming a southward-tilted neotectonic block with subsidence near the Northern Giona Fault and uplift near the Ypati fault to the north. These two E-W faults represent younger structures disrupting the older NNW-trending tectonic framework. Fault scarps are observed all along the 14 km length of the Northern Giona fault accompanied by cataclastic zones, separating the carbonate formations of the Parnassos Unit from thick scree, slide blocks, boulders and olistholites. Inversion of fault-slip data has shown a mean slip vector of 45°, N004°E, which aligns with the current regional extensional deformation of the area, as confirmed by focal mechanism solutions. Based on the general asymmetry of the alpine units in the hanging wall, we interpret a listric fault geometry at depth using slip-line analysis and we forward modelled a disrupted fault-propagation fold using kinematic trishear algorithms, estimating a total displacement of 6500 m and a throw of approximately 2000 m. Seismic activity in the area of the Northern Giona Fault includes a magnitude 6.1 earthquake in 1852, which caused casualties, rockfalls and extensive damage, as well as a magnitude 5.1 event in 1983. The expected seismic magnitude is deterministically estimated between 6.2 and 6.7, depending on the potential westward continuation of the Northern Giona Fault beyond the Mornos River to the Northern Vardoussia saddle. The seismic hazard zone includes several villages located near the fault, particularly on the hanging wall, where intense landslide activity during seismic events could result in severe damage to regional infrastructure. The neotectonic development of the Northern Giona Fault highlights the importance of extending seismotectonic research into the mountainous regions of central Greece within the alpine formations, beyond the post-orogenic sedimentary basins.

Glacier velocity and surge detection in the Karakoram region, Pakistan: using remotely sensed data with cross-correlation feature tracking

ABSTRACT This research addresses the knowledge gap regarding glacier surging detection (GSD) and their potential downstream implications for Glacier Lake Outburst Floods (GLOFs) risk. This study investigates GSD across the Karakoram region, Pakistan, focusing on 30 glaciers from 2013 to 2023. The increasing occurrence of irregular and rapid glacial surges poses significant threats to downstream communities, the potential formation of ice dam lakes, and subsequent outburst floods. High-resolution satellite imagery, DEM, temperature, and precipitation data quantified glacier velocity rate (GVR) using feature-tracking, surge detection, and correlations. Findings indicate substantial movement ≥42 m/y during 2015–19 and 2021–22, peaking at 56.98 m/y in 2018–19; with significant Z-Scores, surges were recorded in KG-01, KG-06, KG-07, KG-19, KG-29, and KG-30. The region witnessed significant elevation changes, with a positive change at the terminus of KG-01, KG-06, KG-07, and KG-29 and a negative at the glacier’s accumulation zones. Furthermore, climatic factors, including rising average temperatures (17°C to 20°C) and precipitation (14 to 30 mm/y), significantly influenced glacier velocity, affecting glaciers by 20-43% and 38-59%, respectively. These findings underscore the pivotal role of surge velocities in shaping glacier outlets and influencing lake drainage, potentially leading to GLOFs.

Mannitol versus mannitol with hypertonic saline for brain relaxation during craniotomies using ultra-sonographic optic nerve sheath diameter

ABSTRACT Background This study compared the effect of conventional doses of mannitol alone versus combined lower doses of mannitol-hypertonic saline on brain debulking during elective craniotomies. Patients and methods Sixty participants aged 18–60 years, ASA class I or II, who were scheduled for elective supratentorial brain tumor surgery, were randomly separated into 2 equal groups. Group (M) received 5 ml/kg of 20% mannitol at the onset of the surgical incision over 15 min. Group (MH) received 2.5 ml/kg of 20% mannitol plus 2.5 ml/kg 3% hypertonic saline (HTS) at the onset of the surgical incision over 15 min. Optic nerve sheath diameter (ONSD), brain relaxation score, serum lactate, electrolytes, and surgeon’s satisfaction were measured. Results Both groups yielded similar results concerning demographic and tumor characteristics. The Optic nerve sheath diameter (ONSD) was considerably lower in group MH compared to group M just before and immediately after dural incision (p = <0.001, and 0.001) respectively. The brain relaxation was considerably more adequate in group MH when compared to group M (p = 0.001). Group MH showed significant elevation in serum sodium, chloride, and osmolarity at 60 min and at the end of surgery with negligible changes at 12- and 24-hrs postoperatively. Moreover, group M showed a significant increase in serum potassium and lactate at 60 min and at the end of surgery, with insignificant change at 12- and 24-hrs postoperatively. Surgeons were more noteworthy satisfied in group MH. Conclusion Optic nerve sheath was comparable to brain relaxation score (BRS) for assessing the brain relaxation. In comparison to mannitol alone, lower prescribed doses of mannitol in combination with hypertonic saline (HTS) have provided better intraoperative brain debulking, clinically accepted electrolyte changes, and more surgeons’ satisfaction during supratentorial brain tumor surgery.

Assessment of the Expression Levels of USP27X and DDX3X genes in Systemic Lupus Erythematosus (SLE) Patients

Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease influencing numerus tissues in body. Ubiquitin carboxyl-terminal hydrolase 27 (USP27X) is a deubiquitinating enzyme involved in the type I interferons (IFNs) generation, apoptosis and production of proinflammatory mediators. DEAD-box helicase 3 X-linked (DDX3X) is a ribonucleic acid (RNA) helicases and contributes to the generation of type I IFNs, and proinflammatory mediators. Considering the involvement of IFN type I, apoptotic cell death and proinflammatory mediators in the pathogenesis of SLE, the expression levels of USP27X and DDX3X genes were assessed in SLE patients. Methods: Two groups, including SLE patients and healthy subjects, were included in the study and the expression levels of USP27X and DDX3X genes in their peripheral blood mononuclear cells (PBMC) were quantified by the real-time polymerase chain reaction (PCR). Results: The results demonstrated the expression level of DDX3X gene was 5.9-fold higher in the SLE patients compared to the healthy subjects ( P &lt; .01). No significant difference in the expression level of USP27X gene was detected between both groups ( P &gt; .05). Conclusion: A significant elevation in the level of DDX3X gene in SLE patients prepossess the potential involvement of DDX3X in SLE pathogenesis possibly through the induction of proinflammatory mediators. In spite of the potential involvement of USP27X in SLE through the induction of type 1 IFNs, and apoptotic cell death, our finding did not provide evidence in the contribution of USP27X in SLE pathogenesis.

Risk of renal dysfunction in patients with dengue fever: a case-control study

Dengue fever, a mosquito-borne infection, is typically caused by the Dengue virus, leading to various illnesses, including dengue fever and severe dengue fever. This study aims to investigate the outcome of dengue fever severity as renal dysfunction in patients. For this case-control study, blood samples of the patients (N=66), including 31 D-W (Dengue without warning signs), 20 D+W (Dengue with warning signs), and 15 SDF (Severe dengue fever), as well as controls (N=45) of same age groups, were obtained. The renal parameters were determined and statistically analyzed using a one-way ANOVA and chi-square/Fisher exact test. The intergroup comparison showed that phosphorous, calcium, and sodium presented a marked decrease (P &lt; 0.001) in dengue patient groups compared to controls. However, a significant increase (P &lt; 0.05) in chloride was indicated in dengue patient groups. Moreover, a prominent potassium reduction (P = 0.036) was observed in the dengue subjects group compared to controls. Among the renal parameters, creatinine presented a significant elevation (P &lt; 0.002) while uric acid was significantly (P = 0.004) dropped in dengue patients groups as compared to controls. This study's results suggest that dengue infection's severity may be associated with aberrant electrolyte imbalance and renal impairment. This study indicates that dengue affects normal kidney functions and harms the patients' health. Keywords: electrolytes; renal profile; dengue fever; severe dengue fever

Effect of upper eyelid blepharoplasty with or without orbicularis oculi muscle removal on anterior segment parameters, keratometry, and ocular biometry.

To evaluate the effect of upper eyelid blepharoplasty with or without the removal of a strip of orbicularis oculi muscle on corneal topographic parameters, anterior segment parameters, intraocular pressure, and ocular biometry. This prospective study examined 428 eyes of 214 patients with dermatochalasis. Patients were divided into two groups randomly: those who underwent orbicularis oculi muscle excision (Group 1) during blepharoplasty and those who did not (Group 2). Following a detailed ophthalmological examination, corneal topography was used to evaluate the eyes anterior chamber depth (ACD), iridocorneal angle (ICA), keratometry measurements, and corneal astigmatism (CA) in the preoperative and postoperative first and third months. Ocular biometry was used to assess axial length (AXL) and intraocular lens (IOL) power. Goldmann applanation tonometry was used to measure intraocular pressure (IOP). The age and gender distribution between the groups were similar (p = 0.595 and p = 0.493, respectively). In Group 1, the mean steep keratometry (K2) value increased by 1.1 D and the mean CA increased by 0.81 D in the first month (p < 0.001 for both comparisons). The increases in K2 and CA were 0.7 D and 0.63 D, respectively, in Group 2 (p < 0.001 and p = 0.004, respectively). At the postoperative third month, both groups demonstrated statistically significant persistent elevations in K2 and CA values (p < 0.05 for all comparisons) compared to preoperative measurements. Group 1 exhibited statistically significant decreases in both IOL power calculations (0.43 D according to the Barrett formula and 0.40 D according to the SRK/T formula, p < 0.001, for both) and ICA (38.1 ± 4.7° vs. 35.8 ± 4.1°, p = 0.009) measurements at the only one-month postoperative follow-up. IOP, AXL, and ACD measurements did not exhibit any significant changes in both groups at the first and third postoperative months. In addition to changes in keratometry and CA, blepharoplasty with muscle excision significantly decreased IOL power and ICA. It may be beneficial to inquire about recent blepharoplasty history and the surgical technique employed in patients scheduled for cataract or refractive surgery.

High intracranial pressure following endoscopic third ventriculostomy: illustrative case.

Endoscopic third ventriculostomy (ETV) is an effective procedure for the treatment of triventriculomegaly associated with aqueductal stenosis. However, some patients can develop severe and symptomatic intracranial pressure (ICP) elevations in the immediate postoperative period that can be monitored and treated with external ventricular drain (EVD) placement and controlled cerebrospinal fluid (CSF) diversion until the ICP normalizes and symptoms resolve. The authors describe the case of a 39-year-old male who underwent ETV and intraoperative EVD placement for obstructive hydrocephalus associated with aqueductal stenosis. The patient was noted to have sustained ICP elevations in the immediate perioperative period but ultimately experienced a successful clinical outcome without requiring a ventriculoperitoneal shunt. Significant sustained ICP elevations in the immediate postoperative period following ETV can occur and may indicate a prolonged adjustment period. These elevations can be tolerated if the patient's symptoms and ICP are well controlled, with temporary external CSF diversion if the patient becomes symptomatic, as the ICP will likely normalize with a reassuring clinical outcome. https://thejns.org/doi/10.3171/CASE24478.

Study the Relationship of IFN-γ (+874A/ T) Polymorphism, and Some Cytokines with Breast Cancer in a Population from Baghdad City, Iraq

Background: Breast cancer is still a complicated and common health issue that affects millions of people globally. Aim: the current investigation aimed to study the relationship of IFN-γ (+874 A/T) genetic polymorphism, and some cytokines to breast cancer women in a population from Baghdad city/ Iraq. Materials and Methods: In this study, (80) females with an age of (20-60) years were employed; they were attending Oncology Teaching Hospital, Medical City, Baghdad. All these females were notified regarding the purpose of these investigations and agreed to its protocol. 80 healthy women were taken into the current study for comparison purposes. Results: The findings demonstrated that C3 levels showed a significant (P≤0.05) elevation in patients compared to healthy females. C4 levels demonstrated significantly (P≤0.05) elevation in patients that compared to healthy females. IL-6 levels significantly (P &lt;0.05) increased in patients compared with control group (4.15±0.65 pg/ml). IL-17 concentration in serum of patients showed a significant (P &lt;0.05) increased in patients compared with healthy ones. T and A alleles of IFN-γ T / A +874 locus had distinct results when repeated distribution was used to compare women who had breast cancer to healthy individuals. In the patient BC sample, the T allele was 42.4%, while the allele T in the control group was 71.4%. While the allele A in the sample of BC patients, which is 57.6%, compared to the allele A in control group, which was 28.6%. Conclusions: This study suggests that elevated IL-6 and IL-17 levels, along with specific IFN-γ gene polymorphisms, could serve as potential biomarkers for breast cancer risk and prognosis.

The impact of different treatments on thromboelastography and other conventional parameters in patients with colorectal cancer

ObjectiveTo comprehend the effects of diverse therapeutic interventions on thromboelastography (TEG) and conventional coagulation parameters among individuals diagnosed with colorectal cancer, this study aims to explore the clinical relevance of both thromboelastography and conventional coagulation metrics in evaluating coagulation function and predicting the incidence of thrombotic and hemorrhagic events in patients with colorectal cancer.MethodsA cohort of 122 patients with colorectal cancer retrospectively recruited and divided into 2 groups: those undergoing surgical intervention (operation group) and those not subjected to surgery (non-operation group). According to the different types of treatment they received, the operation group was divided into chemotherapy-only group and a group receiving a combination of targeted therapy and chemotherapy. Blood samples were collected on admission and subjected to coagulation parameter assessment, including conventional coagulation tests and thromboelastography (TEG) assessment. Receiver operating characteristic (ROC) analysis was performed to predict the occurrence of complications in patients with colorectal cancer.ResultsCompared with the operation group, the non-operation group showed significant reductions in reaction time(R-time) and kinetics time (K-time), and significant elevation in angle, maximum amplitude (MA), fibrinogen and platelets. Patients receiving targeted therapy and chemotherapy had lower angle and maximum amplitude and higher R-time and K-time, activated partial thromboplastin time and fibrinogen. The area under the curve for TEG in patients without treatment was 0.802. The area under the curve for TEG and conventional coagulation parameters were 0.654 and 0.660 respectively.ConclusionDiverse treatments distinctly impact on the coagulation indicators of individuals diagnosed with colorectal cancer. The coagulation parameters observed in patients prior to operation suggest a hypercoagulable state. Nevertheless, following postoperative chemotherapy and targeted therapy, this hypercoagulable state demonstrates a notable improvement, occasionally leading to a propensity for hypocoagulation. The findings of this investigation underscore the unique clinical importance of thromboelastography (TEG) alongside traditional coagulation parameters, demonstrating that these diagnostic tools possess complementary value and cannot be substituted interchangeably.

The neuropathological basis of elevated serum neurofilament light following experimental concussion

Mild traumatic brain injury (mTBI) or concussion is a substantial health problem globally, with up to 15% of patients experiencing persisting symptoms that can significantly impact quality of life. Currently, the diagnosis of mTBI relies on clinical presentation with ancillary neuroimaging to exclude more severe forms of injury. However, identifying patients at risk for a poor outcome or protracted recovery is challenging, in part due to the lack of early objective tests that reflect the relevant underlying pathology. While the pathophysiology of mTBI is poorly understood, axonal damage caused by rotational forces is now recognized as an important consequence of injury. Moreover, serum measurement of the neurofilament light (NfL) protein has emerged as a potentially promising biomarker of injury. Understanding the pathological processes that determine serum NfL dynamics over time, and the ability of NfL to reflect underlying pathology will be critical for future clinical research aimed at reducing the burden of disability after mild TBI. Using a gyrencephalic model of head rotational acceleration scaled to human concussion, we demonstrate significant elevations in serum NfL, with a peak at 3 days post-injury. Moreover, increased serum NfL was detectable out to 2 weeks post-injury, with some evidence it follows a biphasic course. Subsequent quantitative histological examinations demonstrate that axonal pathology, including in the absence of neuronal somatic degeneration, was the likely source of elevated serum NfL. However, the extent of axonal pathology quantified via multiple markers did not correlate strongly with the extent of serum NfL. Interestingly, the extent of blood–brain barrier (BBB) permeability offered more robust correlations with serum NfL measured at multiple time points, suggesting BBB disruption is an important determinant of serum biomarker dynamics after mTBI. These data provide novel insights to the temporal course and pathological basis of serum NfL measurements that inform its utility as a biomarker in mTBI.

The amino acid metabolism pathway of peripheral T lymphocytes and ketamine-induced schizophrenia-like phenotype.

The intricate interplay between peripheral adaptive immune cells and the central nervous system (CNS) has garnered increasing recognition. Given that alterations in cell quantities often translate into modifications in metabolite profiles and that these metabolic changes can potentially traverse the bloodstream and enter the CNS, thereby modulating the progression of mental illnesses, we sought to explore the metabolic profiles of peripheral immune cells in a ketamine-treated mouse model of schizophrenia. We used flow cytometry to scrutinize the alterations in peripheral adaptive immune cells in a ketamine-induced schizophrenia mouse model. Subsequently, we implemented an untargeted metabolomic approach with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to detect the metabolite profiles of peripheral abnormal lymphocytes and identify differential metabolites present in plasma. We then employed targeted metabolomics using UPLC-MS/MS to quantify the common differential metabolites detected in mouse plasma. Flow cytometry analysis detected a notable increase in the count of peripheral CD3+ T cells in a ketamine-induced schizophrenia mouse model. Subsequent untargeted metabolomics analysis revealed that the amino acid metabolism pathway underwent substantial alterations. A detailed quantification of 22 amino acid profiles in the peripheral plasma indicated significant elevation in the levels of glycine, alanine, asparagine, and aspartic acid. Our ongoing research has yet to conclusively identify the precise amino acid metabolism pathway that serves as the pivotal factor in the manifestation of the schizophrenia-like phenotype induced by ketamine. The peripheral amino acid metabolism pathway is involved in the ketamine-induced schizophrenia-like phenotype. The metabolic profile of peripheral immune cells could provide accurate biomarkers for the diagnosis and treatment of psychiatric diseases.

Therapeutic potency of kaempferol against Naja haje venom induced neurotoxicity, inflammation, biological activities, and antioxidant system damage: a pre-clinical antivenom evaluation.

Naja haje envenoming manifests organ system disorders leading to severe fatalities due to the venom's toxins. The neutralizing capacity of kaempferol has been reported against some medically significant snake venoms with exception of N. haje venom (NhV). This current study assessed the neutralizing profile of kaempferol against toxicities induced by NhV using in vitro and in vivo methods. In in vitro, NhV induced wide spectrum of toxic biological activities with substantial increase in hemorrhagic, anticoagulating, and hemolytic effects. Likewise in the in vivo study, the venom caused hematological disorders by inducing acute anemia, thrombocytopenia, and leucopenia in envenomed rats. Also, the venom caused detrimental effect on the antioxidant defense system of the brain through significant (P < 0.05) elevation of malondialdehyde (MDA), nitrite (NIT), and suppression of reduce glutathione (GSH) antioxidant, superoxide dismutase (SOD), catalase (CAT), and glutathione transferase (GST) enzymes. Additionally, the levels of neurotoxicity biomarkers, monoamine oxidase (MAO) and acetylcholinesterase (AChE), and pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were significantly (P < 0.0.5) enhanced by NhV in the brain of envenomed rats. Severe pathohistological effects were observed in brain tissues of the envenomed rats. However, kaempferol substantially (P < 0.05) inhibited the NhV-induced biological activities, normalized the hematological disorders, enhanced antioxidants system functions, and significantly (P < 0.05) suppressed the levels of neurotoxicity biomarkers and pro-inflammatory cytokines. Severe structural alterations observed in the brain tissues were ameliorated after kaempferol treatment. Further exploration of kaempferol could lead to the development of an alternative therapy for treatment of N. haje envenoming.

Impact of a Three-Month Training Break on Swimming Performance in Athletes with Intellectual Disability

This study aimed to ascertain whether there were any differences in anthropometrics, heart rate, and swimming performance parameters in athletes with intellectual disabilities (ID) before and after a three-month training break. A total of 21 athletes participated in the study, comprising 16 males and 5 females, with a mean age of 28.3 ± 8.7 years. All participants had ID, and six of them had Down syndrome. The study participants were classified as S14 athletes from a local swimming club. All participants had a minimum of four years of swimming experience and attended two to three one-hour sessions per week for eight consecutive months. All athletes completed two trials of 25 m freestyle swimming, one at the end of a training session and the other at the beginning of a new session. The measurements included weight, body mass index (BMI), handgrip strength (HGS), heart rate (pre- and post-trial), performance (T25), stroke count (SC), stroke length (SL), stroke rate, and the SWOLF efficiency index. The results demonstrated statistically significant elevations in weight (80.2 ± 16.1 to 81.7 ± 15.9), BMI (26.8 ± 5.5 to 27.2 ± 5.5), T25 (33.1 ± 17.1 to 35.6 ± 18), SC (19.3 ± 6.1 to 20.7 ± 7.2), and SWOLF (52.4 ± 22.0 to 56.3 ± 25.2) and a reduction in SL (1.39 ± 0.48 to 1.27 ± 0.42). However, no significant differences were observed in the remaining parameters. Significant correlations were found for body weight, BMI, HGS, and SWOLF with T25 throughout the study. It was concluded that individuals with ID experienced a decline in 25 m swimming performance due to technical rather than physiological factors after three months of detraining.

Yohimbine treatment improves pulmonary fibrosis by attenuating the inflammation and oxidative stress via modulating the MAPK pathway

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disorder characterized by the accumulation of extracellular matrix and collagen, resulting in significant parenchymal scarring and respiratory failure that leads to mortality. Yohimbine (YBH) is an α-2 adrenergic receptor antagonist with anti-oxidant and anti-inflammatory properties. In the current study, we aimed to investigate the anti-inflammatory, anti-oxidant and anti-fibrotic activity of YBH against LPS/TGF-β-induced differentiation in BEAS-2B/LL29 cells and bleomycin (BLMN) induced pulmonary fibrosis model in rats. Network pharmacology, gene expression, Western-blot analysis, immune-cytochemistry/immunohistochemistry, lung function and histology techniques were used to assess the fibrotic marker expression/levels in cells or rat lung tissues. YBH treatment significantly attenuated the LPS-induced pro-inflammatory (identified through a network-pharmacology approach) and oxidative stress markers expression in lung epithelial cells. TGF-β stimulation significantly elevated the fibrotic cascade of markers and treatment with YBH attenuated these markers’ expression/levels. Intra-tracheal administration of BLMN caused a significant elevation of various inflammatory/oxidative stress and fibrotic markers expression in lung tissues and treatment with YBH significantly mitigated the same. Ashcroft score analysis revealed that BLMN exhibited severe distortion of the lungs, elevation of thickness of the alveolar walls and accumulation of collagen in tissues, further treatment with YBH significantly suppressed these events and improved the lung architecture. Lung functional parameters demonstrated that BLMN-induced stiffness and resistance were reduced considerably upon YBH treatment and restored lung function dose-dependently. Overall, this study reveals that YBH treatment significantly attenuated the BLMN-induced fibrosis by regulating the MAPK pathway and provided insightful information for progressing towards translational outcomes.

"Polyethylene Terephthalate Nanoplastics Caused Hepatotoxicity in Mice Can be Prevented by Betaine: Molecular and Immunohistochemical Insights".

Polyethylene terephthalate nanoplastics (PET-NPs) are one of the most frequently distributed nanoplastics in daily life. Betaine is thought to be a promising hepatoprotective agent. The current investigation focused on whether orally administered PET-NPs caused hepatotoxicity and ameliorative effect of betaine. Forty adult male Swiss albino mice were randomly split into four groups: group I control, group II betaine (1000 mg/kg I/P), group III PET-NPs (200 mg/kg orally), and group IV betaine plus PET-NPs at doses similar to group II& III respectively. After 30 days, blood sample were collected then animals were euthanized and liver specimens were dissected out for biochemical and histopathological examination. PET-NPs induced a significant elevation in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA), as well as an increase in the inflammatory genes a proto-oncogene (c-FOS) and cyclooxygenase 2 (COX2) (p ≤ 0.05), with a substantial decrease in glutathione (GSH) (p ≤ 0.05). Furthermore, on the level of histopathological analysis PET-NPs caused alterations in hepatic tissue architecture as vascular dilatation and congestion with hepatocytes degeneration, bile duct epithelial hyperplasia and inflammatory cell infiltrations While on the level of immunohistochemistry, PET-NPs trigger positive tumor necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-ҠB) expression in comparison to control. Meanwhile, betaine treatment reduced the deleterious effects of PET-NPs. To summarize, PET-NPs may cause hepatotoxicity in mice, with a belief that betaine could mitigate the detrimental impact.

Utilization of Ziziphus spina-christi leaf extract-loaded chitosan nanoparticles in wastewater treatment and their impact on animal health

Ziziphus leaf extract (ZEX), chitosan nanoparticles (CS NPs) and Ziziphus leaf extract loaded chitosan nanoparticles (ZEX-CS NPs) were prepared in this study and after chemical analysis and characterization, they were used in wastewater purification. The study also aimed to establish, using an animal model, the feasibility of employing treated water in drinking applications. ZEX-CS NPs were prepared by ionic gelation method. About 25 male Sprague Dawley rats (10 weeks and 170-200 g) were divided into five groups (5 rats/group): group I received tape water; group II received untreated wastewater, group III received ZEX treated wastewater, group IV received CS NPs treated wastewater and group V received ZEX-CS NPs treated wastewater. ZEX-CS NPs have a size of 73 nm, hydrodynamic size of 85.81 nm and zeta potential of −33.68 mV. In addition, ZEX-CS NPs have stronger antioxidant and anti-inflammatory activity with moderate anti-coagulant activity and weaker cytotoxicity than ZEX and CS NPs. Group II showed a significant elevation in the kidney function parameters, oxidative stress and cytokine levels when compared to the other groups, in addition; no significant differences were found in all measured parameters between the rats of group I and V. ZEX-CS NPs were effective in wastewater purification.

Serum protein risk stratification score for diagnostic evaluation of metabolic dysfunction–associated steatohepatitis

Background: Reliable, noninvasive tools to diagnose at-risk metabolic dysfunction–associated steatohepatitis (MASH) are urgently needed to improve management. We developed a risk stratification score incorporating proteomics-derived serum markers with clinical variables to identify high-risk patients with MASH (NAFLD activity score &gt;4 and fibrosis score &gt;2). Methods: In this 3-phase proteomic study of biopsy-proven metabolic dysfunction–associated steatotic fatty liver disease, we first developed a multi-protein predictor for discriminating NAFLD activity score &gt;4 based on SOMAscan proteomics quantifying 1305 serum proteins from 57 US patients. Four key predictor proteins were verified by ELISA in the expanded US cohort (N = 168) and enhanced by adding clinical variables to create the 9-feature MASH Dx score, which predicted MASH and also high-risk MASH (F2+). The MASH Dx score was validated in 2 independent, external cohorts from Germany (N = 139) and Brazil (N = 177). Results: The discovery phase identified a 6-protein classifier that achieved an AUC of 0.93 for identifying MASH. Significant elevation of 4 proteins (THBS2, GDF15, SELE, and IGFBP7) was verified by ELISA in the expanded discovery and independently in the 2 external cohorts. MASH Dx score incorporated these proteins with established MASH risk factors (age, body mass index, ALT, diabetes, and hypertension) to achieve good discrimination between MASH and metabolic dysfunction–associated steatotic fatty liver disease without MASH (AUC: 0.87—discovery; 0.83—pooled external validation cohorts), with similar performance when evaluating high-risk MASH F2-4 (vs. MASH F0-1 and metabolic dysfunction–associated steatotic fatty liver disease without MASH). Conclusions: The MASH Dx score offers the first reliable noninvasive approach combining novel, biologically plausible ELISA-based fibrosis markers and clinical parameters to detect high-risk MASH in patient cohorts from the United States, Brazil, and Europe.

Association between 25(OH) vitamin D and multiple sclerosis: cohort, shared genetics, and Causality

BackgroundMultiple Sclerosis (MS), an autoimmune disorder causing demyelination and neurological damage, has been linked to 25-hydroxyvitamin D (25OHD) levels, suggesting its role in immune response and MS onset. This study used GWAS datasets to investigate genetic associations between 25OHD and MS.MethodsWe utilized a large-scale prospective cohort to evaluate serum 25OHD levels and MS risk. Linkage Disequilibrium Score Regression (LDSC) assessed genetic correlations between 25OHD levels and MS. Cross-trait genome-wide pleiotropy analysis revealed shared genetic loci. MAGMA analysis identified pleiotropic genes, enriched tissues, and gene sets. Stratified LDSC estimated tissue-specific and cell-specific heritability enrichment, and multi-trait co-localization analysis identified shared immune cell subsets. Bidirectional Mendelian Randomization (MR) assessed the causal association between 25OHD and MS risk.ResultsThe observational study found a nonlinear relationship between 25OHD levels and MS risk, with the lowest quartile showing significant risk elevation. Our findings revealed shared genetic structure between 25OHD levels and MS, suggesting a common biological pathway involving immune function and CNS integrity. We found 24 independent loci shared between 25OHD levels and MS risk, enriched in brain tissues and involved in pathways like LDL, HDL, and TG metabolism. Four loci (6p24.3, 6p22.2, 12q14.1, and 19p13.2) had strong co-localization evidence, with mapped genes as potential drug targets. Bidirectional MR analysis supported a causal effect of 25OHD levels on MS risk, suggesting 25OHD supplementation could modulate MS risk.ConclusionThis study reveals the complex relationship between 25OHD levels and MS, indicating that higher levels are not always advantageous and recommending moderation in supplementation. We identified SMARCA4 as a potential therapeutic target and detailed key pathways influencing this interaction.Graphical

Potential of dehydroepiandrosterone and quercetin to ameliorate copper oxide nanoparticles induced hepatotoxicity in albino wistar rats.

The current investigation was designed as an experimental endeavor to explore the protective efficacy of dehydroepiandrosterone (DHEA) and quercetin against hepatotoxicity induced by copper oxide (CuO) nanoparticles. Rats were subjected to CuO nanoparticle intoxication through intraperitoneal injection of 150mg/kg b.w. for three weeks, followed by the administration of the aforementioned antioxidants for an additional three weeks. This study systematically tracked alterations in liver enzymatic activity, antioxidant levels, apoptotic markers, and histopathological changes using the comet assay. CuO nanoparticle-intoxicated rats exhibited a significant increase in serum alanine transaminase aspartate aminotransferase (AST), and bilirubin levels, coupled with a noteworthy reduction in serum albumin. Moreover, there was a marked rise in serum tumor necrosis factor-alpha levels, concomitant with a significant decline in serum hepatocyte growth factor (HGF). Caspase-3 and Bax mRNA levels in the serum showed a substantial increase, while serum Bcl-2 mRNA levels witnessed a significant decrease. Liver tissue levels of malondialdehyde (MDA) and nitric oxide (NOx) experienced a significant elevation, and DNA damage was observed through the comet assay. Histopathological examination of the liver tissue substantiated these aforementioned findings. Administration of the antioxidants DHEA or quercetin, either individually or in combination, mitigated the parameters of hepatotoxicity to varying extents. In summary, the hepatic genotoxicity induced by CuO nanoparticles demonstrated improvement following the administration of either DHEA or quercetin. Additionally, their combined administration exhibited a more potent protective potential.