Search Results (30)

Hepatocellular injury syndrome represents a pathological process with a broad etiological spectrum, including viral infections, autoimmune diseases, or intoxications. Clinicians must identify the potential cause using both anamnestic data and available paraclinical examinations. We present the case of a 55-year-old female patient, admitted to the Internal Medicine 1 Department at the Clinical County Emergency Hospital Bihor, Oradea, Romania. The patient exhibited nonspecific complaints and insignificant pathological antecedents, but from a biochemical perspective, substantial changes in liver transaminase levels were evident. To establish differential diagnoses, a series of biochemical and immunological tests were performed, along with a thorough medical history. It was concluded that the patient regularly consumes herbal infusions, specifically Laurus nobilis leaves, commonly known as Bay Laurel. Although this might be easily overlooked at first glance, a closer examination could explain the current clinical picture. In April 2024, a 55-year-old female patient with no history of liver pathology was admitted. She complained of asthenia fatigue, anorexia, mixed dyspeptic symptoms, diffuse abdominal pain, and a weight loss of 12 kg. The pathology had insidiously started approximately 3 months prior. On examination, the patient had altered general status, anorexia, and was overweight. Biochemically, the patient had elevated liver transaminase values (AST = 196 U/L and ALT = 357 U/L) that continued to rise during hospitalization, despite hepatoprotective treatment. Various paraclinical examinations were performed to exclude other potential causes of hepatic aggression, having excluded ordinary causes. Consequently, a liver biopsy was performed, and the histopathological examination leaned toward a toxic hepatitis etiology. Application of the updated RUCAM scale yielded a score of eight points (“probable” HILI—Herb-Induced Liver Injury). Clinical and biochemical improvement was observed after complete cessation of bay leaf tea consumption. This case highlights the potential hepatotoxicity of commonly used culinary herbs when consumed in large quantities or as concentrated infusions and emphasizes the importance of detailed anamnesis regarding herbal product use. Full article

Concrete structures develop several defects as the structure ages. One of the common concerns in structural integrity is the formation of cracks, which demands regular inspection with precision. In this study, a bridge underpass arch structure was inspected with the help of an Unmanned Aerial Vehicle (UAV) in a coastal region of the Mediterranean Sea, where 2D captured images were transferred into a 3D model for better visualisation from a Structural Health Monitoring (SHM) perspective. The images with cracks were manually annotated, using the VGG tool, by an expert. Using the 3DF Zephyr software, from sparse to dense point clouds, and 3D mesh to orthophoto, all 3D models were constructed from the annotated and unannotated images of the structure. The 3D model achieved a Ground Sampling Distance of 0.0046 m/pixel, with an image alignment of 60%. The Bundle Adjustment Mean Reprojection Error confirmed satisfactory internal model accuracy. The final assessment through the orthophoto, where a resolution of 4531 × 2433 pixels was achieved, revealed that the images were of sufficient quality to capture the details and the defects present, and better visualisation could be made. This output demonstrates that UAV-based photogrammetry is time- and cost-efficient and surpasses the traditional visual inspection of confined structures. Full article

Herb-induced liver injury (HILI) is an increasingly recognized cause of liver damage, associated with the widespread global use of herbal products. Despite its rising incidence, HILI remains underrecognized and underreported due to the absence of specific biomarkers, limited regulatory oversight, and the complexity of multi-ingredient formulations. Diagnostic efforts rely heavily on the Roussel Uclaf Causality Assessment Method (RUCAM), with clinical presentations often nonspecific and dominated by hepatocellular patterns of injury. Epidemiological data demonstrate regional variation, with notably higher case numbers in Asia and the Americas. Mechanistically, HILI may result from either intrinsic (predictable, dose-dependent) or idiosyncratic (unpredictable, immune-mediated) reactions. Genetic predispositions, including certain HLA alleles, have been identified as risk factors. Hepatotoxicity is often linked to specific phytochemicals such as pyrrolizidine alkaloids, catechins, anthraquinones, and diterpenoids, which may contribute to oxidative stress, mitochondrial damage, or immune activation. Additionally, product inconsistencies and contamination complicate risk assessment and safety evaluation. Current management focuses on immediate discontinuation of the suspected product and supportive care, though severe cases may require liver transplantation. Future directions include the development of specific diagnostic tools, implementation of globally harmonized regulatory standards, improved pharmacovigilance systems, and enhanced public and professional education. Addressing these priorities is crucial for reducing HILI-related morbidity while supporting the safe use of herbal therapies. Full article

Objectives: The present study investigated proclivity for non-consensual intimate-image distribution and its related dimensions—enjoyment and acceptance—in relation to key demographic and relational variables, including gender, age, sexual orientation, frequency of dating app use, and current romantic relationship status. Methods: A total of 1735 Greek university students (mean age = 22 years, standard deviation = 6.18; 35.2 percent male) participated in an anonymous online survey. Pearson correlation analyses and multiple linear regression models were conducted to examine the associations and predictive value of the demographic variables on proclivity, enjoyment, and acceptance of non-consensual intimate-image distribution. Results: Men, younger participants, and those who reported more frequent use of dating applications or websites demonstrated higher proclivity for non-consensual intimate-image distribution. Gender and frequency of dating app use were also significant predictors of enjoyment, with men and frequent users reporting greater enjoyment. Regarding acceptance, sexual orientation was the only significant predictor, with non-heterosexual individuals indicating higher levels of acceptance. Romantic relationship status did not significantly predict any of the three outcome variables. Conclusions: These findings highlight the significance of gender, age, sexual orientation, and dating app engagement in understanding the psychological and behavioral dimensions of non-consensual intimate-image distribution. The results support the need for targeted prevention efforts and further research into the contextual and psychosocial factors associated with this form of image-based abuse. Full article

Introduction: The third step in histidine degradation is catalysed by imidazolonepropionase. It catalyses the conversion of 4-imidazolone-5-propionic acid to produce N-formimino-L-glutamic acid by hydrolyzing the carbon-nitrogen bonds. The histidine is a very expensive amino acid inside the cell and its degradation is a very conserved process. To date, very few reports are there regarding the structure of bacterial imidazolonepropionase but no reports have been published regarding the comparative structure and sequence analysis of this enzyme from bacterial sources. Methods: An in-silico study has been done to characterize the imidazolonepropionase from gram-positive Bacillus subtilis and gram-negative Agrobacterium fabrum. Results: The sequence analysis revealed that a higher amount of charged residues are present in Bacillus subtilis. These charged residues help in the increment of polarity and hydrophilicity of Bacillus subtilis. The formation of intra-protein interactions was also high in gram-positive species. Interestingly, both species have almost equal abundance of aromatic amino acids in their sequences, but the formation of aromatic-aromatic interactions was high in Bacillus subtilis. Finally, the molecular dynamics simulation study revealed that imidazolonepropionase from Bacillus subtilis was more stable and compact than Agrobacterium fabrum. Conclusions: The imidazolonepropionase from Bacillus subtilis was more stable than Agrobacterium fabrum. Due to the presence of higher stable imidazolonepropionase in Bacillus subtilis, it can use histidine more efficiently. Full article

Spinal cord injury (SCI) triggers microglial/monocytes activation with distinct pro-inflammatory or inflammation-resolving phenotypes, which potentiate tissue damage or facilitate functional repair, respectively. The major integrin Mac-1 (CD11b/CD18), a heterodimer consisting of CD11b and CD18 chains, is expressed in multiple immune cells of the myeloid lineage. Here, we examined the effects of CD11b gene ablation in neuroinflammation and functional outcomes after SCI. qPCR analysis of C57BL/6 female mice showed upregulation of CD11b mRNA starting from 1 d after injury, which persisted up to 28 d. CD11b knockout (KO) mice and their wildtype littermates were subjected to moderate SCI. At 1 d post-injury, qPCR showed increased expression of genes involved with inflammation-resolving processes in CD11b KO mice. Flow cytometry analysis of CD45^intLy6C⁻CX3CR1⁺ microglia, CD45^hiLy6C⁺Ly6G⁻ monocytes, and CD45^hiLy6C⁺Ly6G⁺ neutrophils revealed significantly reduced cell counts as well as reactive oxygen species (ROS) production in CD11b KO mice at d3 post-injury. Further examination with NanoString and RNA-seq showed upregulation of pro-inflammatory genes, but downregulation of the ROS pathway. Importantly, CD11b KO mice exhibited significantly improved locomotor function, reduced cutaneous mechanical/thermal hypersensitivity, and limited tissue damage at 8 weeks post-injury. Collectively, our data suggest an important role for CD11b in regulating tissue inflammation and functional outcome following SCI. Full article

Herbal and complementary medicine are frequently integrated with conventional medicine. We aim to report a case of severe herbal-induced liver injury (HILI) due to chronic use of green tea and protein shake. We present both clinical and laboratory evidence implicating mitochondrial toxicity and an immune response leading to a hypersensitivity reaction to the products. We have recently treated a 39-year-old man with hepatotoxicity resulting from a combination of a green tea-containing powder and a branched-chain amino acid supplement that was commenced 2 months previously. The hepatotoxicity resolved by stopping the consumption of these products and no other cause was detected. We decided to perform a lymphocyte toxicity assay (LTA) to determine if there was laboratory support for this diagnosis. LTA (% toxicity) represents the response of the mitochondria to toxic injury. To determine the role of the proinflammatory and anti-inflammatory cytokines and chemokines in the patient’s reaction, we measured the level of cytokines and chemokine in the media of growing cells, exposed to each product or to a combination of products. The increased cytokines and chemokines are presented as the x-fold elevations from the upper limit of normal (ULN) for matrix metalloproteinase (MMP) (pg/mL × 1.5 ULN) and interleukin (IL)-1β (pg/mL × 1.8 ULN). Higher elevations were found for interferon (IFN)-β, IFN-γ, IL-8, IL 13, IL-15 (pg/mL × 2 ULN), regulated upon activation, normal T cell expressed and presumably secreted (RANTES) (pg/mL × 2 ULN), and nuclear factor (NFκB) (pg/mL × 3 ULN). The highest increases were for vascular endothelial factor (VEGF) (pg/mL × 10 ULN), tumor necrosis factor (TNF)-α, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (pg/mL × 13 ULN). An examination of cellular markers showed the difference between programmed cell death (apoptosis) and cell death due to necrosis. In our case, cytokeratin—ccK18 (M-30) U/L was within the normal limits, suggesting that apoptosis was normal, while ccK8(M65) U/L was elevated at 1.5 × ULN. This result implies that upon the treatment of the patient’s lymphocytes with the products, the mechanism of toxicity is necrosis. In susceptible individuals, the combination of protein and herbal tea produces mitochondrial toxicity and a strong T-lymphocyte-1 response, leading to HILI. There is a need of international reporting of adverse drug reactions by clinicians, laboratories, and pharmaceutical manufacturers to drug regulatory authorities. This requires internationally accepted standard definitions of reactions, as well as criteria for assessment. Full article

Herbal-induced liver injury (HILI) continues to increase in prevalence each year due to the ongoing popularity of herbal supplements and complementary and alternative medicines. A detailed literature review of case reports and clinical studies published from March 2021 to March 2023 was performed. We discuss the epidemiology and diagnosis of HILI as well as the current and proposed laws and regulations. The 2021 ACG guidelines and 2022 AASLD practice guidelines for the diagnosis and management of drug and herbal-induced liver injury are discussed. We describe updates to previously reported etiologies of HILI such as ayurveda, ashwagandha, turmeric, kratom, green tea extract, and garcinia cambogia. Newly described supplements resulting in HILI, such as tinospora cordifolia, horse chestnut, alkaline water, and more, are described. We discuss newly and previously identified hepatoprotective herbal supplements as they have been reported in the study of animal models and human liver cells. This review suggests the need for ongoing research on the causes and mechanisms of HILI to ensure its proper diagnosis, prevention, and treatment in the future. The goal of this review is to provide novice and expert readers with knowledge regarding the possible etiologies of HILI and a general overview. Full article

RuBisCO is the main photosynthetic enzyme of carbon assimilatory pathways in nature. Despite being the most abundant protein on earth, RuBisCO is still relatively underutilised in the food chain. Although there are sequence and structure details in the database, there are few instances of studies on evolutionary relationships. A bioinformatics and in silico study was conducted to check sequence and structural differences of RuBisCO among different photosynthetic organisms. RuBisCO from Oryza sativa showed an abundance of charged amino acids, salt-bridges, and intra-protein interactions and was more hydrophilic in nature compared to Nostoc sp., Chlamydomonas reinhardtii, and Nicotiana tabacum. From molecular dynamics simulations, lower root mean square deviation and root mean square fluctuation indicate that RuBisCO from Oryza sativa was more stable, followed by Nicotiana tabacum, and a lower radius of gyrations indicates their tight packing. From this study, it was clear that some specific evolutions in charged amino acids of RuBisCO of monocot, i.e., Oryza sativa, make it more stable and stronger than other plant groups. The study concludes that a more stable nature of RuBisCO is gained from monocot Oryza sativa. Full article

Herb-induced liver injury (HILI) caused by herbal supplements, natural products, and products used in traditional medicine are important for differential diagnoses in patients with acute liver injury without an obvious etiology. The root of Withania somnifera (L.) Dunal, commonly known as ashwagandha, has been used in Ayurvedic medicine for thousands of years to promote health and longevity. Due to various biological activities, ashwagandha and its extracts became widespread as herbal supplements on the global market. Although it is generally considered safe, there are several reported cases of ashwagandha-related liver injury, and one case ended with liver transplantation. In this paper, we review all reported cases so far. Additionally, we describe two new cases of ashwagandha hepatotoxicity. In the first case, a 36-year-old man used ashwagandha capsules (450 mg, three times daily) for 6 months before he developed nausea, pruritus, and dark-colored urine. In the second case, a 30-year-old woman developed pruritus after 45 days of using ashwagandha capsules (450 mg). In both cases, serum bilirubin and liver enzymes (aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were increased. The liver injury pattern was hepatocellular (R-value 11.1) and mixed (R-value 2.6), respectively. The updated Roussel Uclaf Causality Assessment Method (RUCAM) (both cases with a score of seven) indicated a “probable” relationship with ashwagandha. Clinical and liver function improvements were observed after the discontinuation of ashwagandha supplement use. By increasing the data related to ashwagandha-induced liver injury, these reports support that consuming ashwagandha supplements is not without its safety concerns. Full article

Clinical and mechanistic considerations in idiosyncratic drug-induced liver injury (iDILI) remain challenging topics when they are derived from mere case narratives or iDILI cases without valid diagnosis. To overcome these issues, attempts should be made on pathogenetic aspects based on published clinical iDILI cases firmly diagnosed by the original RUCAM (Roussel Uclaf Causality Assessment Method) or the RUCAM version updated in 2016. Analysis of RUCAM-based iDILI cases allowed for evaluating immune and genetic data obtained from the serum and the liver of affected patients. For instance, strong evidence for immune reactions in the liver of patients with RUCAM-based iDILI was provided by the detection of serum anti-CYP 2E1 due to drugs like volatile anesthetics sevoflurane and desflurane, partially associated with the formation of trifluoroacetyl (TFA) halide as toxic intermediates that form protein adducts and may generate reactive oxygen species (ROS). This is accompanied by production of anti-TFA antibodies detected in the serum of these patients. Other RUCAM-based studies on serum ANA (anti-nuclear antibodies) and SMA (anti-smooth muscle antibodies) associated with AIDILI (autoimmune DILI) syn DIAIH (drug-induced autoimmune hepatitis) provide additional evidence of immunological reactions with monocytes as one of several promoting immune cells. In addition, in the blood plasma of patients, mediators like the cytokines IL-22, IL-22 binding protein (IL-22BP), IL-6, IL-10, IL 12p70, IL-17A, IL-23, IP-10, or chemokines such as CD206 and sCD163 were found in DILI due to anti-tuberculosis drugs as ascertained by the prospective updated RUCAM, which scored a high causality. RUCAM-based analysis also provided compelling evidence of genetic factors such as HLA (human leucocyte antigen) alleles contributing to initiate iDILI by a few drugs. In conclusion, analysis of published RUCAM-based iDILI cases provided firm evidence of immune and genetic processes involved in iDILI caused by specific drugs. Full article

Disrupted behavior and respiratory distress effects of 96-h acute deltamethrin exposures in adult Mozambique tilapia, Oreochromis mossambicus, were investigated using behavioral indices and opercular movement, respectively. Deltamethrin concentrations were found to be associated with toxicological (lethal and sublethal) responses. At 24, 48, 72, and 96 h, the LC50 values and 95% confidence limits were 12.290 (11.174–14.411 µg/L), 12.671 (11.334–15.649 µg/L), 10.172 (9.310–11.193 µg/L), and 8.639 (7.860–9.417 µg/L), respectively. The GUTS-model analysis showed that GUTS-SD (stochastic death) with a narrow tolerance distribution in deltamethrin exposed O. mossambicus populations was more sensitive than the GUTS-IT (individual tolerance) model. Prior to death, exposed fish demonstrated concentration-dependent mortality and disturbed behavioral responses, including uncoordinated swim motions, increased mucus secretion, unbalanced and unpredictable swimming patterns, and inactivity. The altered behavioral patterns and increased opercular movement with increased deltamethrin levels and exposure time are strongly suggestive of neurotoxicity and respiratory distress, respectively. Adverse Outcome Pathways (AOPs), describing biological mechanisms and plausible pathways, highlighted oxidative stress and cholinergic effects as intermediate steps linked to respiratory distress and behavioral toxicity. Full article

Macrophages are present in every tissue in the body and play essential roles in homeostasis and host defense against microorganisms. Some tissue macrophages derive from the yolk sac/fetal liver that populate tissues for life. Other tissue macrophages derive from monocytes that differentiate in the bone marrow and circulate through tissues via the blood and lymphatics. Circulating monocytes are very plastic and differentiate into macrophages with specialized functions upon entering tissues. Specialized monocyte/macrophage subsets have been difficult to differentiate based on cell surface markers. Here, using a combination of “pan” monocyte/macrophage markers and flow cytometry, we asked whether myeloperoxidase (MPO) could be used as a marker of pro-inflammatory monocyte/macrophage subsets. MPO is of interest because of its potent microbicidal activity. In wild-type SPF housed mice, we found that MPO⁺ monocytes/macrophages were present in peripheral blood, spleen, small and large intestines, and mesenteric lymph nodes, but not the central nervous system. Only monocytes/macrophages that expressed cell surface F4/80 and/or Ly6C co-expressed MPO with the highest expression in F4/80^HiLy6C^Hi subsets regardless of tissue. These cumulative data indicate that MPO expression can be used as an additional marker to differentiate between monocyte/macrophage subsets with pro-inflammatory and microbicidal activity in a variety of tissues. Full article

Herb-induced liver injury (HILI) can be caused by supplements containing herbs, natural products, and products used in traditional medicine. Herbal products’ most common adverse reaction is hepatotoxicity. Almost every plant part can be used to make herbal products, and these products can come in many different forms, such as teas, powders, oils, creams, capsules, and injectables. HILI incidence and prevalence are hard to estimate and vary from study to study because of insufficient large-scale prospective studies. The diagnosis of HILI is a challenging process that requires not only insight but also a high degree of suspicion by the clinician. HILI presents with unspecific symptoms and is a diagnosis of exclusion. For diagnosis, it is necessary to make a causality assessment; the Council for International Organizations of Medical Sciences assessment is the preferred method worldwide. The most effective treatment is the suspension of the use of the suspected herbal product and close monitoring of liver function. The objective of this review is to highlight the necessary steps for the clinician to follow to reach a correct diagnosis of herb-induced liver injury. Further studies of HILI are needed to better understand its complexity and prevent increased morbidity and mortality. Full article