A document by Ijeoma Orabueze. Click on the document to view its contents.

Geodorum laxiflorum Griff. (Orchidaceae) is relectotypified here by superseding Bhatt & al. (2015) and by designating a CAL-specimen as lectotype of G. laxiflorum, as the lectotype designated by Bhatt & al. (2015) for the name is found erroneous. Morphological variations along with an overlooked character of the labellum of this Indian endemic and vulnerable species of orchid are presented based on study of livespecimens collected in the wild for the first time from two Indian states. Further, the name Eulophia diffusiflora M.W. Chase, Kumar & Schuit. is synonymised under G. laxiflorum until Eulophia R. Br. is conserved against Geodorum Andrews.

Tubulointerstitial fibrosis is an inevitable consequence of all progressive chronic kidney disease (CKD) and contributes to a substantial health burden worldwide. Icariin, an active flavonoid glycoside obtained from Epimedium species, exerts potential antifibrotic effect. The study aimed to explore the protective effects of icariin against tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO)-induced CKD mice and TGF-β1-treated HK-2 cells, and furthermore, to elucidate the underlying mechanisms. The results demonstrated that icariin significantly improved renal function, alleviated tubular injuries, and reduced fibrotic lesions in UUO mice. Furthermore, icariin suppressed renal inflammation, reduced oxidative stress as evidenced by elevated SOD activity and decreased MDA level. Additionally, TOMM20 immunofluorescence staining and transmission electron microscope revealed that mitochondrial mass and morphology of tubular epithelial cells in UUO mice was improved by icariin. In HK-2 cells treated with TGF-β1, icariin markedly decreased profibrotic proteins expression, inhibited inflammatory factors, and protected mitochondria along with improving mitochondrial morphology, reducing reactive oxygen species (ROS) and mitochondrial ROS (mtROS) overproduction, and preserving membrane potential. Further investigations demonstrated that icariin could activate Nrf2/HO-1 pathway both in vivo and in vitro, whereas inhibition of Nrf2 by ML385 counteracted the protective effects of icariin on TGF-β1-induced HK-2 cells. In conclusion, icariin protects against renal inflammation and tubulointerstitial fibrosis at least partly through Nrf2-mediated attenuation of mitochondrial dysfunction, which suggests that icariin could be developed as a promising therapeutic candidate for the treatment of CKD.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with variable disease courses and multiple clinical manifestations [1]. The etiology of SLE is not clear, but different environmental (ultraviolet [UV] light, infections, drugs), genetic, and hormonal factors all seem to be involved [1]. Positive family history and history of having other autoimmune illnesses are considered high-risk factors for SLE, but most SLE cases are scattered [1]. The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as a mandatory entry criterion; followed by additive weighted standards grouped in seven clinical (constitutional, hematological, neuropsychiatric, serosal, musculoskeletal, renal, mucocutaneous ) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10, and patients accumulating ≥10 points are classified to have SLE [2]. Herein, we report this case of neuropsychiatric lupus as it is uncommon and is a severe form of SLE.

The low incidence of vincristine-induced peripheral neuropathy (VIPN) in Kenyan children may result from low vincristine exposure. We performed a pharmacokinetically (PK) guided dose-escalation feasibility study of vincristine in Kenyan children (NCT05844670). Vincristine PK exposure was assessed with a previously developed nomogram. A 20% dose increase was recommended for participants with low exposure and no VIPN, hyperbilirubinemia or malnutrition. None of the fifteen participants developed VIPN. Low vincristine exposure was seen in only one participant: a dose increase was implemented without side-effects. Average vincristine exposure was high. In conclusion, the participants did not develop VIPN despite having high vincristine exposure.

Behçet syndrome (BS) is a chronic, multisystemic inflammatory condition with unanswered questions regarding its pathogenesis and rational therapeutics. A microarray-based comparative transcriptomic analysis was performed to elucidate the molecular mechanisms of BS and identify any potential therapeutic targets. Twenty-nine BS patients (B) and 15 age and sex-matched control subjects (C) were recruited. Patients were grouped as mucocutaneous (M), ocular (O), and vascular (V) according to their clinical phenotypes. GeneChip Human Genome U133 Plus 2.0 arrays were used for expression profiling on peripheral blood samples of the patients and the control subjects. Following documentation of the differentially expressed gene (DEG) sets, the data were further evaluated with bioinformatics analysis, visualization, and enrichment tools. Validation of the microarray data was performed using qRT-PCR. When P ≤0.05 and fold change ≥2.0 were chosen, the following numbers of DEGs were obtained; B vs. C: 28, M vs. C: 20, O vs. C: 8, V vs. C: 555, M vs. O: 6, M vs. V: 324, O vs. V: 142. Venn diagram analysis indicated only two genes, CLEC12A and IFI27, in the intersection of M vs. C and O vs. C and V vs. C. Another noteworthy gene appeared as CLC in the DEG sets. Cluster analyses successfully clustered distinct clinical phenotypes of BS. While innate immunity-related processes were enriched in the M group, adaptive immunity-specific processes were significantly enriched in the O and V groups. Distinct clinical phenotypes of BS patients displayed distinct expression profiles. In Turkish BS patients, expression differences regarding the genes CLEC12A, IFI27, and CLC seemed to be operative in the disease pathogenesis. Based on these findings, future research should consider the immunogenetic heterogeneity of BS clinical phenotypes. Two anti-inflammatory genes, namely CLEC12A and CLC, may be valuable as therapeutic targets and may also help design an experimental model in BS.

Bovine colostrum is a rich source of bioactive compounds, including growth factors, that may promote tissue regeneration. Studies suggest it has potential therapeutic benefits in humans, but further research is needed to fully understand its mechanisms of action. This study aims to review scientific articles on the use of bovine colostrum as a bioactive agent for tissue regeneration in humans and twelve articles were selected. In vitro studies show that bovine colostrum can benefit cells by reducing cell proliferation and inducing differentiation. The concentration of colostrum used has a direct impact on the results, with no positive results observed at some high concentrations (20%). Extracted portions of colostrum (EVs and IMF) showed better results than the complete colostrum. In vivo studies show that bovine colostrum is a promising natural source for wound healing, as its bioactive factors help in the orderly progression of the healing process. However, some studies did not find any benefit related to tissue regeneration, and more research is needed to explore the full potential of colostrum in regenerative medicine and to develop more effective therapies for wound healing.

A document by Sabthagi Sivathasan. Click on the document to view its contents.

Deterioration of lung diffusion capacity during childhood in sickle cell diseaseWord count: 1500To the Editor,The American Society of Hematology guidelines, 2019, recommended obtaining pulmonary function tests (PFTs) in patients with sickle cell disease (SCD) with various respiratory symptoms even if they are at their steady state.1 These guidelines acknowledged that the usefulness of routine PFT is unknown because of the lack of research. However, this society further suggested that if the PFTs are obtained, it should be a comprehensive study including lung volumes and lung-diffusing capacity for carbon monoxyde (DLCO), in addition to spirometry.1 A large study in adult patients (n=310) with SCD showed that pulmonary function is abnormal in 90% of adult patients with Hb-SS.2 Common abnormalities included restrictive physiology and decreased DLCO. In this study, decreased DLCO indicated more severe sickle vasculopathy characterized by impaired hepatic and renal function, and a negative linear correlation existed between DLCO and age, suggesting that in adults with Hb-SS, disruption of alveolar–capillary gas exchange progressively deteriorated with time.2 Two recent cross-sectional studies of children with SCD showed that pulmonary function, including DLCO, worsened with age and showed correlations with biological markers of inflammation (induced sputum IL‐6 levels or blood neutrophilia).3,4Overall, these studies highlight the potential interest of DLCO measurement in SCD. The DLCO is the product of KCO (carbon monoxide coefficient of transfer) and alveolar volume (VA) and these two latter indices need to be interpreted separately since the decrease in DLCO is often mitigated by a preserved KCO or even increased KCO in SCD. It has been demonstrated that when corrected for hemoglobin levels, the children with SCD compared to controls of similar age had elevated KCOcorrected. The determination of alveolar-capillary membrane conductance (Dm) and pulmonary capillary blood volume (Vc) from the lung diffusing capacity for carbon monoxide (DLCO) or for nitric oxide (DLNO) has been done in SCD since the seventies, demonstrating an increase in Vc in SCD. KCO is mathematically linked to both Dm and Vc (1/KCO = VA/Dm + VA/θVc); thus, the increase in KCO is related to Vc increase, but since DLCO has been shown to worsen with age, the changes of DLCO, VA and KCO over time in children with SCD deserve to be studied.The objectives of our study were to describe the evolution of DLCO and its determinants, KCO and VA, and to further assess the initial risk factors of the decrease in DLCO in children/adolescents with SCD. To this end, we retrospectively recorded the routine follow-up PFTs of children with SCD who were included in a prospective cross-sectional study that included the measurement of both DLCO and DLNO with the calculation of Dm and Vc.5

Background: Kawasaki disease (KD) is a kind of vasculitis with an unidentified etiology. Cathelicidin (LL-37) may be involved in the development of the KD process; therefore, further research to investigate the molecular mechanism of LL-37 involvement in KD is warranted. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of TNF-α, IL-1β, NLRP3, and LL-37 in the sera of healthy subjects, children with KD, and children with pneumonia. Subsequently, human recombinant LL-37 or/and TLR4-specific inhibitor TAK-242 stimulated HCAECs cells, CCK-8 was used to detect cell proliferation, flow cytometry to detect apoptosis, transmission electron microscopy to observe cytoskeletal changes, Transwell to measure cell migration ability, ELISA to detect inflammatory factor levels, Western blotting to analyze protein levels of TLR4 and NF-κB p-65, and qRT-PCR to determine LL-37, NLRP3 mRNA levels. Results: In this study, we found that the level of LL-37 was highly expressed in the serum of children with KD, and after LL-37 stimulation, apoptosis was significantly increased in HCAECs, and the expression levels of TLR4, NLRP3 and inflammatory factors in cells were significantly enhanced. Intervention with the TLR4-specific inhibitor TAK-242 significantly alleviated the LL-37 effects on cellular inflammation, TLR4, NLRP3 promotion effect. Conclusions: Our data suggest that LL-37 induces an inflammatory response in endothelial cells via TLR4-NF-κB, leading to coronary artery injury in KD, providing a potential target to treat KD.

Trypanosoma cruzi, a flagellated protozoan, is the causative agent of Chagas disease. The parasite has developed various mechanisms to get through its intricate life cycle and adapt to different evolutionary phases. T. cruzi proliferates in the insect vector’s digestive tract as an epimastigote form, encountering fluctuating nutrient availability and oxidative stress caused by the digestion of red blood cells from the mammalian host blood meal. To unravel how the parasite’s metabolism adapts to these changing conditions, we conducted an analysis of the chemical species present in epimastigote forms. This involved comparing cultured parasites with those subjected to nutritional deficiency or oxidative stress using untargeted metabolomics. We looked at twenty-one samples: seven biological copies of parasites that were actively growing, seven samples that were put in a medium without nutrients for three hours, and seven samples that were treated with glucose oxidase for thirty minutes to make H 2O 2 continuously. Importantly, in all conditions, parasite viability was maintained when the samples were collected. Upon nutrient removal, we observed a substantial decrease in amino acids and carbohydrate metabolites, accompanied by the accumulation of fatty acids and steroids, with the predominance of inositol and sphingolipid metabolism, along with a simultaneous decrease in the levels of H 2O 2. In the presence of H 2O 2, a significant rise in components of the pentose pathway and specific amino acids such as methionine and serine occurred, along with pathways related to an increase in antioxidant species metabolism such as ribulose 5-phosphate and glyceric acid. Conversely, fatty acid and steroid levels decrease. We found no common increase in metabolites or lipids. In contrast, eight species (succinic acid, glutamic acid, valine, 2-hydroxyisocaproic acid, alanine, indolelactic acid, proline, and lanosterol) were consumed under both stresses. These findings underscore the rapid and distinct enrichment responses in amino acids, lipids, and carbohydrates required to cope with each different environmental condition. This information not only enhances our understanding of T. cruzi’s metabolic flexibility but also opens avenues for studying cellular metabolism changes in diverse environments used by the parasite.

Background: Ulcerative colitis (UC) is a chronic inflammatory disease caused by abnormal immune system reactions resulting in inflammation and ulcers in the large intestine. Phillygenin (PHI) is a natural compound found in Forsythia suspensa (Thunb.) Vahl, known for its various bioactivities, including anti-inflammatory, anti-obesity, and antipyretic activities. However, the potential anti-inflammatory effects of PHI on UC and its underlying mechanisms are still poorly understood. Methods: In this study, we investigated the therapeutic effects of PHI on acute UC induced by DSS and TNBS. We evaluated the effects of PHI on disease activity index, body weight, mortality, intestinal mucosal barrier, cytokine secretion, and macrophage infiltration into colon tissue using various techniques such as flow cytometry, immunofluorescence, ELISA, RT-qPCR, and Western blotting. Results: Our findings revealed that PHI has therapeutic properties in UC treatment. PHI was able to maintain body weight, reduce disease activity index and mortality, restore the intestinal mucosal barrier, and inhibit cytokine secretion. Flow cytometry assay and immunofluorescence indicated that PHI reduces macrophage infiltration into colon tissue. Additionally, both in vivo and in vitro results suggested that PHI may exert anti-inflammatory effects by downregulating the TLR4/MyD88/NF-κB pathway, inhibiting NLRP3 inflammasome activation. Conclusion: In conclusion, PHI possesses anti-inflammatory properties and has the potential as a therapeutic agent for the treatment of UC. Our study provides insights into the underlying mechanisms of PHI’s therapeutic effects and highlights the potential for further research in developing PHI-based treatments for UC.

The most typical pathological change in Alzheimer’s disease (AD) is the aggregated deposition of amyloid-β (Aβ). APOE ε3/ε3 is the most prevalent genotype in the AD population. Individuals with amyloid-PET (Aβ-PET) positivity (+) and disease progression may not be a minority in the APOE ε3/ε3 non-demented population. This study searched for accessible and available clinical models that can predict Aβ-PET (+), and assess factors that can predict clinical conversion in APOE ε3/ε3 non-demented individuals. We selected 293 non-demented individuals with APOE ε3/ε3 from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. They were divided into Aβ-PET (+) and Aβ-PET (-) groups based on the 18F-florbetapir PET SUVR cut-off value of >1.11. Stepwise regression and the receiver operating characteristic curve (ROC) were used to search for a single or a combination of clinical variables, and to assess the accuracy of clinical markers, respectively. The Cox regression model was used to explore the risk factors associated with clinical transition. Our study found that the combination of clinical markers (Model A4: sex, education, ventricle and WMH volume; Model D5: everyday cognition study-partner total (EcogSPTotal) score, age, plasma p-tau 181 and WMH) respectively predicted Aβ-PET status in cognitively normal (CN) individuals and mild cognitive impairment (MCI) individuals. Aβ-PET (+) and EcogSPTotal score were independent predictors of clinical transition in APOE ε3/ε3 non-demented individuals. These specific factors offered an attractive and cost-effective assessment for Aβ status and clinical conversion.

Patterns of pathogen prevalence are, at least partially, the result of coevolutionary host-pathogen interactions. Thus, exploring the distribution of host genetic variation in relation to infection by a pathogen within and across populations can provide important insights into mechanisms of host defence and adaptation. Here we use a landscape genomics approach (Bayenv) in conjunction with genome-wide data (ddRADseq) to test for associations between avian malaria (Plasmodium) prevalence and host genetic variation across 13 populations of the island endemic Berthelot’s pipit (Anthus berthelotii). Considerable and consistent spatial heterogeneity in malaria prevalence was observed among populations over a period of 15 years. The prevalence of malaria infection was also strongly positively correlated with pox (Avipoxvirus) prevalence. Multiple host loci showed significant associations with malaria prevalence after controlling for genome-wide neutral genetic structure. These sites were located near to or within genes linked to metabolism, stress response, transcriptional regulation, complement activity and the inflammatory response, many previously implicated in vertebrate responses to malarial infection. Our findings identify diverse genes - not just limited to the immune system - that may be involved in host protection against malaria and suggests that spatially variable pathogen pressure may be an important evolutionary driver of genetic divergence among wild animal populations, such as Berthelot’s pipit. Further, our data indicate that spatio-temporal variation in multiple different pathogens (e.g., malaria and pox in this case) may have to be studied together to develop a more holistic understanding of host pathogen-mediated evolution.

Pollution from toxic spores has caused us a lot of problems, because spores are extremely resistant and can survive most disinfectants. Therefore, the detection of spore response to disinfectant is of great significance for the development of effective decontamination strategies. In this work, we investigated the effect of 0.5% sodium hypochlorite on the molecular and morphological properties of single spores of Bacillus subtilis using single-cell techniques. Laser tweezers Raman spectroscopy showed that sodium hypochlorite resulted in Ca 2+-dipicolinic acid release and nucleic acid denaturation. Atomic force microscopy showed that the surface of treated spores changed from rough to smooth, protein shells were degraded at 10 min, and the permeability barrier was destroyed at 15 min. The spore volume decreased gradually over time. Live-cell imaging showed that the germination and growth rates decreased with increasing treatment time. These results provide new insight into the response of spores to sodium hypochlorite.

Taxonomic monographs, such as those of the Fauna and Flora of the Gulf of Naples, have almost eternal life, in terms of scientific relevance, and keep being cited even after centuries.

This study analyzes how national intersectoral public policy experiences have been adopted and implemented using a Health in All Policies (HiAP) approach in the past two decades. It seeks to provide evidence on enabling factors that triggered three effective intersectoral public policies to improve population health in Mexico by improving nutritional, educational, and healthcare access conditions, reducing road traffic injuries, and addressing obesogenic feeding practices. We followed a qualitative approach to analyze the three intersectoral public policies selected as case studies. First, we designed an analytical framework to assess how intersectoral public policies are adopted, implemented, and sustained. The proposed framework is based on peer-reviewed articles and grey public policy literature. Second, we used information from eleven semi-structured interviews to key stakeholders conducted in previous research to identify more specific enablers and barriers of the three intersectoral policies selected according to predefined analytical categories used in the questionnaire. The analysis showed three overall key findings. First, sound empirical evidence is essential for adopting a HiAP approach. Second effective intersectoral mechanisms enhance implementation feasibility. Third, results-based monitoring and evaluation contribute to the continuity of the analyzed intersectoral public policies. Finally, political support is needed throughout the policy process to maintain governance capacity and deliver results. Finally, we drew five global policy lessons that may be applicable in similar public policy settings in other countries. First, both technical and political enablers help set the intersectoral agenda. Second, effective communication is instrumental in convincing all stakeholders to address public health-related policy issues. Third, political support at the highest level possible and the federal government’s capacity are essential to implement sound policies. Fourth, several enablers exist for enhancing collaboration between ministries during implementation. Finally, monitoring and evaluation results are necessary for sustaining intersectoral policies beyond administrations.

Title: Secondary Syphilis Presenting as Fever of Unknown OriginAuthors: Hannah Eloise Wilding, BS1; Amy Hays, MD2