bluuebunny/crossref_metadata_2025_split huggingface dataset:
Huiyang Shengji decoction promotes wound healing in diabetic mice by activating the EGFR/PI3K/ATK pathway
Authors: Liu Qingwu , Zhang Jinchao , Han Xuyang , Chen Jia , Zhai Yating , Lin Yan , Ma Huike , Feng Fang , He Xiujuan , Li Ping 
Published: November 2021

Abstract
Background
Common chronic wounds include diabetic ulcers, venous ulcers, and pressure ulcers. The traditional Chinese medicine Huiyang Shengji decoction (HYSJD) has been shown to promote the healing of diabetic chronic wounds, however, its pharmacological mechanism is still unclear.

Purpose
This study aimed to determine the mechanism of HYSJD in promoting the healing of diabetic chronic skin ulcers.

Methods
Ultra-performance liquid chromatography was combined with tandem mass spectrometry (UPLC-MS/MS) to analyze the main components of HYSJD and the absorbed components in mouse serum at 30 min after oral administration of HYSJD. db/db mouse models for chronic skin ulcers were constructed by full-thickness skin resection. Wound tissues at day 7 post wound formation were used to perform microarray analysis of growth factors and chemokine expression. GO and KEGG enrichment analysis was performed on differentially expressed proteins. ELISA assays were used to measure differential expressed cytokines in the serum and Western blot analysis was used to determine the expression levels of related pathway proteins in the skin wounds.

Results
UPLC-MS/MS analysis showed that the main chemical components of HYSJD were flavonoids, terpenes, alkaloids, phenylpropanoids, and carbohydrates. At 30 min after oral administration of HYSJD, five absorbed components were detected in the serum, these included formononetin, calycosin, hypaconitine, calycosin-7-glucoside, and sinapic acid. HYSJD was found to increase the wound healing rate in chronic skin ulcers in db/db mice at days 3, 7, and 14 post wound formation, and promote the proliferation of epidermal cells. Two proteins that were differentially expressed between the different groups, i.e., IGF-1 and EGFR, were further validated. Serum ELISA assays showed that serum EGFR in the HYSJD treatment group was significantly increased. KEGG pathway analysis suggested that the PI3K/AKT pathway involved in HYSJD promoting the proliferation of epidermal cells in chronic wounds in db/db mice. Experimental verification showed that HYSJD activated the PI3K/AKT signaling pathway in mouse wound skin.

Conclusion
HYSJD promotes the proliferation of epidermal cells in chronic diabetic wounds by increasing EGFR expression in the wounds and activating the PI3K/AKT signaling pathway. Our study provides an experimental basis for the pharmacological mechanism of HYSJD.
Arachidonic acid drives adaptive responses to chemotherapy-induced stress in malignant mesothelioma
Authors: Cioce Mario , Canino Claudia , Pass Harvey , Blandino Giovanni , Strano Sabrina , Fazio Vito Michele 
Published: November 2021

AbstractBackgroundHigh resistance to therapy and poor prognosis characterizes malignant pleural mesothelioma (MPM). In fact, the current lines of treatment, based on platinum and pemetrexed, have limited impact on the survival of MPM patients. Adaptive response to therapy-induced stress involves complex rearrangements of the MPM secretome, mediated by the acquisition of a senescence-associated-secretory-phenotype (SASP). This fuels the emergence of chemoresistant cell subpopulations, with specific gene expression traits and protumorigenic features. The SASP-driven rearrangement of MPM secretome takes days to weeks to occur. Thus, we have searched for early mediators of such adaptive process and focused on metabolites differentially released in mesothelioma vs mesothelial cell culture media, after treatment with pemetrexed.MethodsMass spectrometry-based (LC/MS and GC/MS) identification of extracellular metabolites and unbiased statistical analysis were performed on the spent media of mesothelial and mesothelioma cell lines, at steady state and after a pulse with pharmacologically relevant doses of the drug. ELISA based evaluation of arachidonic acid (AA) levels and enzyme inhibition assays were used to explore the role of cPLA2 in AA release and that of LOX/COX-mediated processing of AA. QRT-PCR, flow cytometry analysis of ALDH expressing cells and 3D spheroid growth assays were employed to assess the role of AA at mediating chemoresistance features of MPM. ELISA based detection of p65 and IkBalpha were used to interrogate the NFkB pathway activation in AA-treated cells.ResultsWe first validated what is known or expected from the mechanism of action of the antifolate. Further, we found increased levels of PUFAs and, more specifically, arachidonic acid (AA), in the transformed cell lines treated with pemetrexed. We showed that pharmacologically relevant doses of AA tightly recapitulated the rearrangement of cell subpopulations and the gene expression changes happening in pemetrexed -treated cultures and related to chemoresistance. Further, we showed that release of AA following pemetrexed treatment was due to cPLA2 and that AA signaling impinged on NFkB activation and largely affected anchorage-independent, 3D growth and the resistance of the MPM 3D cultures to the drug.ConclusionsAA is an early mediator of the adaptive response to pem in chemoresistant MPM and, possibly, other malignancies.
Onchocerca volvulus transmission in the Mbam valley of Cameroon following 16 years of annual community-directed treatment with ivermectin, and the description of a new cytotype of Simulium squamosum
Authors: Hendy Adam , Krit Meryam , Pfarr Kenneth , Laemmer Christine , De Witte Jacobus , Nwane Philippe , Kamgno Joseph , Nana-Djeunga Hugues C. , Boussinesq Michel , Dujardin Jean-Claude , Post Rory , Colebunders Robert , O’Neill Sarah , Enyong Peter , Njamnshi Alfred K. 
Published: November 2021

Abstract
Background
The onchocerciasis focus surrounding the lower Mbam and Sanaga rivers, where Onchocerca volvulus is transmitted by Simulium damnosum s.l. (Diptera: Simuliidae), was historically the largest in the southern regions of Cameroon. Annual community-directed treatment with ivermectin (CDTI) has been taking place since 2000, but recent studies have shown that new infections are occurring in children. We aimed to investigate blackfly biting and O. volvulus transmission rates along the lower Mbam river 16 years after the formal onset of annual CDTI.

Methods
Black flies were collected for three consecutive days each month between July 2016 and June 2017 at two riverside villages and two inland sites situated 4.9 km and 7.9 km from the riverside. Specimens collected at each site were dissected on one of the three collection days each month to estimate parity rates and O. volvulus infection rates, while the remaining samples were preserved for pool screening.

Results
In total, 93,573 S. damnosum s.l. black flies were recorded biting humans and 9281 were dissected. Annual biting rates of up to 606,370 were estimated at the riverside, decreasing to 20,540 at 7.9 km, while, based on dissections, annual transmission potentials of up to 4488 were estimated at the riverside, decreasing to 102 and 0 at 4.9 km and 7.9 km, respectively. However, pool screening showed evidence of infection in black flies at the furthest distance from the river. Results of both methods demonstrated the percentage of infective flies to be relatively low (0.10–0.36%), but above the WHO threshold for interruption of transmission. In addition, a small number of larvae collected during the dry season revealed the presence of Simulium squamosum E. This is the first time S. squamosum E has been found east of Lake Volta in Ghana, but our material was chromosomally distinctive, and we call it S. squamosum E2.

Conclusions
Relatively low O. volvulus infection rates appear to be offset by extremely high densities of biting black flies which are sustaining transmission along the banks of the lower Mbam river.

Graphical Abstract
The apolipoprotein receptor LRP3 compromises APP levels
Authors: Cuchillo-Ibañez Inmaculada , Lennol Matthew P. , Escamilla Sergio , Mata-Balaguer Trinidad , Valverde-Vozmediano Lucía , Lopez-Font Inmaculada , Ferrer Isidro , Sáez-Valero Javier 
Published: November 2021

Abstract
Background
Members of the low-density lipoprotein (LDL) receptor family are involved in endocytosis and in transducing signals, but also in amyloid precursor protein (APP) processing and β-amyloid secretion. ApoER2/LRP8 is a member of this family with key roles in synaptic plasticity in the adult brain. ApoER2 is cleaved after the binding of its ligand, the reelin protein, generating an intracellular domain (ApoER2-ICD) that modulates reelin gene transcription itself. We have analyzed whether ApoER2-ICD is able to regulate the expression of other LDL receptors, and we focused on LRP3, the most unknown member of this family. We analyzed LRP3 expression in middle-aged individuals (MA) and in cases with Alzheimer’s disease (AD)-related pathology, and the relation of LRP3 with APP.

Methods
The effects of full-length ApoER2 and ApoER2-ICD overexpression on protein levels, in the presence of recombinant reelin or Aβ42 peptide, were evaluated by microarray, qRT-PCRs, and western blots in SH-SY5Y cells. LRP3 expression was analyzed in human frontal cortex extracts from MA subjects (mean age 51.8±4.8 years) and AD-related pathology subjects [Braak neurofibrillary tangle stages I–II, 68.4±8.8 years; III–IV, 80.4 ± 8.8 years; V–VI, 76.5±9.7 years] by qRT-PCRs and western blot; LRP3 interaction with other proteins was assessed by immunoprecipitation. In CHO cells overexpressing LRP3, protein levels of full-length APP and fragments were evaluated by western blots. Chloroquine was employed to block the lysosomal/autophagy function.

Results
We have identified that ApoER2 overexpression increases LRP3 expression, also after reelin stimulation of ApoER2 signaling. The same occurred following ApoER2-ICD overexpression. In extracts from subjects with AD-related pathology, the levels of LRP3 mRNA and protein were lower than those in MA subjects. Interestingly, LRP3 transfection in CHO-PS70 cells induced a decrease of full-length APP levels and APP-CTF, particularly in the membrane fraction. In cell supernatants, levels of APP fragments from the amyloidogenic (sAPPα) or non-amyloidogenic (sAPPβ) pathways, as well as Aβ peptides, were drastically reduced with respect to mock-transfected cells. The inhibitor of lysosomal/autophagy function, chloroquine, significantly increased full-length APP, APP-CTF, and sAPPα levels.

Conclusions
ApoER2/reelin signaling regulates LRP3 expression, whose levels are affected in AD; LRP3 is involved in the regulation of APP levels.
Fexofenadine: review of safety, efficacy and unmet needs in children with allergic rhinitis
Authors: Meltzer Eli O. , Rosario Nelson Augusto , Van Bever Hugo , Lucio Luiz 
Published: November 2021

AbstractAllergic rhinitis (AR) is the most common undiagnosed chronic condition in children. Moderate/severe AR symptoms significantly impair quality of life, and cause sleep disruption, absenteeism and decreased productivity. Additionally, untreated AR predisposes children to asthma and other chronic conditions. Although intranasal corticosteroids are the most effective pharmacologic treatment for AR, oral antihistamines are often preferred. First-generation antihistamines may be chosen to relieve AR symptoms as they are inexpensive and widely available; however, they cause sedative and cardiovascular negative effects due to poor receptor selectivity. Therefore, second-generation antihistamines were developed to reduce adverse effects while retaining efficacy. There are fewer clinical trials in children than adults, therefore, efficacy and safety data is limited, particularly in children under 6 years, highlighting the need to generate these data in young children with AR. Fexofenadine, a highly selective second-generation antihistamine, effectively alleviates symptoms of AR, is non-sedating due to decreased blood–brain barrier permeability, and is devoid of cardiovascular side effects. Importantly, fexofenadine relieves the ocular symptoms of allergic conjunctivitis, which occur concomitantly with AR, improving quality of life. Overall, fexofenadine displays a favorable safety profile and results in greater treatment satisfaction in children compared with other second-generation antihistamines. This review aimed to evaluate and compare the safety and efficacy of fexofenadine with other available first- and second-generation antihistamines in children with AR.
The first reported case of Blaptica dubia cockroach allergy
Authors: Wangberg Hannah , Mendoza Jun , Gomez Robert , Coop Christopher , White Andrew , Woessner Katharine 
Published: November 2021

Abstract
Background
Periplaneta americana and Blattella germanica cockroaches are widespread, and risk of sensitization increases in urban environments where these roaches thrive as household pests. There are no prior reports of Blaptica dubia cockroach allergy, though human exposure to B. dubia is increasing through commercial breeding as feeder insects.

Case presentation
A 50-year-old B. dubia cockroach breeder presented with progressively worsening upper and lower respiratory symptoms in recent years. Symptoms were worse with exposure to her B. dubia roach colony. Skin prick testing (SPT) to B. dubia cast skin, internal organs, and feces was performed in both the subject and a human control. Testing for P. americana and B. germanica sensitization was also performed in the subject. SDS–Polyacrylamide gel electrophoresis (PAGE), immunoblots, and enzyme-linked immunosorbent assays (ELISA) studies were performed using the subject and control serums to explore for specific IgE binding to B. dubia as well as P. americana. Our results showed SPT was positive to B. dubia internal organs in the subject and negative in the control. In the subject, SPT was negative to P. americana though intradermal (ID) testing was positive and serum specific IgE (sIgE) testing was negative to B. germanica. Immunoblotting of the subject's serum to B. dubia internal organ extract showed several distinct bands of IgE binding at 47 kilodaltons (kD), 68 kD, 74 kD, 83 kD, and 118 kD. The strongest band was at 118 kD on B. dubia immunoblotting, which was absent in P. americana on SDS-PAGE. ELISA studies showed an increased IgE response to both B. dubia and P. americana in the subject versus the control.

Conclusions
This case confirmed the first reported allergy to B. dubia cockroaches. There may be cross-reactivity between B. dubia and P. americana, though our case suggests SPT and sIgE testing using P. americana and B. germanica extract has potential to miss a B. dubia cockroach allergy. This allergy is likely underreported, and further study is needed to explore the natural history of B. dubia cockroach allergy.
Post-coronavirus disease 2019 polyneuropathy with significant response to immunoglobulin therapy: a case report
Authors: Saleh A. , Jung R. , Tonner S. , Hornof F. , Strittmatter M. 
Published: November 2021

Abstract
Background
The symptoms of coronavirus disease 2019, caused by the novel severe acute respiratory syndrome coronavirus 2, were originally assumed to be mainly respiratory. With increasing knowledge, however, it turned out that the spectrum of complaints varies broadly with age and concomitant diseases. While many neurological symptoms were reported in the context of the disease, ranging from permanent fatigue to recurrent headaches and concentration disturbance, treatment approaches are still in development. This case discusses a possible treatment approach with immunoglobulin therapy and its outcomes.

Case presentation
We present the case of a 56-year-old Caucasian female patient who, following coronavirus disease 2019, developed peripheral sensory and autonomic disturbances that fell within subacute demyelinating neuropathy. Because a significant improvement in symptoms as well as in the results of clinical and electrophysiological examination was reported after immunoglobulin therapy, long-term therapy does not appear to be necessary.

Conclusion
Given the significant subjective and objective improvement reported, this case provides additional evidence that immunoglobulin therapy can be considered in post-coronavirus disease 2019 syndrome.
Angiotensin II type 1 receptor agonistic autoantibody blockade improves postpartum hypertension and cardiac mitochondrial function in rat model of preeclampsia
Authors: Booz George W. , Kennedy Daniel , Bowling Michael , Robinson Taprieka , Azubuike Daniel , Fisher Brandon , Brooks Karen , Chinthakuntla Pooja , Hoang Ngoc H. , Hosler Jonathan P. , Cunningham Mark W. 
Published: November 2021

AbstractWomen with preeclampsia (PE) have a greater risk of developing hypertension, cardiovascular disease (CVD), and renal disease later in life. Angiotensin II type I receptor agonistic autoantibodies (AT1-AAs) are elevated in women with PE during pregnancy and up to 2-year postpartum (PP), and in the reduced uterine perfusion pressure (RUPP) rat model of PE. Blockade of AT1-AA with a specific 7 amino acid peptide binding sequence (‘n7AAc’) improves pathophysiology observed in RUPP rats; however, the long-term effects of AT1-AA inhibition in PP is unknown. Pregnant Sprague Dawley rats were divided into three groups: normal pregnant (NP) (n = 16), RUPP (n = 15), and RUPP + ‘n7AAc’ (n = 16). Gestational day 14, RUPP surgery was performed and ‘n7AAc’ (144 μg/day) administered via osmotic minipump. At 10-week PP, mean arterial pressure (MAP), renal glomerular filtration rate (GFR) and cardiac functions, and cardiac mitochondria function were assessed. MAP was elevated PP in RUPP vs. NP (126 ± 4 vs. 116 ± 3 mmHg, p < 0.05), but was normalized in in RUPP + ‘n7AAc’ (109 ± 3 mmHg) vs. RUPP (p < 0.05). PP heart size was reduced by RUPP + ’n7AAc’ vs. RUPP rats (p < 0.05). Complex IV protein abundance and enzymatic activity, along with glutamate/malate-driven respiration (complexes I, III, and IV), were reduced in the heart of RUPP vs. NP rats which was prevented with ‘n7AAc’. AT1-AA inhibition during pregnancy not only improves blood pressure and pathophysiology of PE in rats during pregnancy, but also long-term changes in blood pressure, cardiac hypertrophy, and cardiac mitochondrial function PP.
Protein profile of fiber types in human skeletal muscle: a single-fiber proteomics study
Authors: Murgia Marta , Nogara Leonardo , Baraldo Martina , Reggiani Carlo , Mann Matthias , Schiaffino Stefano 
Published: November 2021

Abstract
Background
Human skeletal muscle is composed of three major fiber types, referred to as type 1, 2A, and 2X fibers. This heterogeneous cellular composition complicates the interpretation of studies based on whole skeletal muscle lysate. A single-fiber proteomics approach is required to obtain a fiber-type resolved quantitative information on skeletal muscle pathophysiology.

Methods
Single fibers were dissected from vastus lateralis muscle biopsies of young adult males and processed for mass spectrometry-based single-fiber proteomics. We provide and analyze a resource dataset based on relatively pure fibers, containing at least 80% of either MYH7 (marker of slow type 1 fibers), MYH2 (marker of fast 2A fibers), or MYH1 (marker of fast 2X fibers).

Results
In a dataset of more than 3800 proteins detected by single-fiber proteomics, we selected 404 proteins showing a statistically significant difference among fiber types. We identified numerous type 1 or 2X fiber type–specific protein markers, defined as proteins present at 3-fold or higher levels in these compared to other fiber types. In contrast, we could detect only two 2A-specific protein markers in addition to MYH2. We observed three other major patterns: proteins showing a differential distribution according to the sequence 1 > 2A > 2X or 2X > 2A > 1 and type 2–specific proteins expressed in 2A and 2X fibers at levels 3 times greater than in type 1 fibers. In addition to precisely quantifying known fiber type–specific protein patterns, our study revealed several novel features of fiber type specificity, including the selective enrichment of components of the dystrophin and integrin complexes, as well as microtubular proteins, in type 2X fibers. The fiber type–specific distribution of some selected proteins revealed by proteomics was validated by immunofluorescence analyses with specific antibodies.

Conclusion
We here show that numerous muscle proteins, including proteins whose function is unknown, are selectively enriched in specific fiber types, pointing to potential implications in muscle pathophysiology. This reinforces the notion that single-fiber proteomics, together with recently developed approaches to single-cell proteomics, will be instrumental to explore and quantify muscle cell heterogeneity.
Evaluation of single domain antibodies as nuclear tracers for imaging of the immune checkpoint receptor human lymphocyte activation gene-3 in cancer
Authors: Lecocq Q. , Debie P. , Puttemans J. , Awad R. M. , De Beck L. , Ertveldt T. , De Vlaeminck Y. , Goyvaerts C. , Raes G. , Keyaerts M. , Breckpot K. , Devoogdt N. 
Published: November 2021

AbstractRecent advancements in the field of immune-oncology have led to a significant increase in life expectancy of patients with diverse forms of cancer, such as hematologic malignancies, melanoma and lung cancer. Unfortunately, these encouraging results are not observed in the majority of patients, who remain unresponsive and/or encounter adverse events. Currently, researchers are collecting more insight into the cellular and molecular mechanisms that underlie these variable responses. As an example, the human lymphocyte activation gene-3 (huLAG-3), an inhibitory immune checkpoint receptor, is increasingly studied as a therapeutic target in immune-oncology. Noninvasive molecular imaging of the immune checkpoint programmed death protein-1 (PD-1) or its ligand PD-L1 has shown its value as a strategy to guide and monitor PD-1/PD-L1-targeted immune checkpoint therapy. Yet, radiotracers that allow dynamic, whole body imaging of huLAG-3 expression are not yet described. We here developed single-domain antibodies (sdAbs) that bind huLAG-3 and showed that these sdAbs can image huLAG-3 in tumors, therefore representing promising tools for further development into clinically applicable radiotracers.
Role of FoxO transcription factors in aging and age-related metabolic and neurodegenerative diseases
Authors: Du Shuqi , Zheng Hui 
Published: November 2021

AbstractAging happens to all of us as we live. Thanks to the improved living standard and discovery of life-saving medicines, our life expectancy has increased substantially across the world in the past century. However, the rise in lifespan leads to unprecedented increases in both the number and the percentage of individuals 65 years and older, accompanied by the increased incidences of age-related diseases such as type 2 diabetes mellitus and Alzheimer’s disease. FoxO transcription factors are evolutionarily conserved molecules that play critical roles in diverse biological processes, in particular aging and metabolism. Their dysfunction is often found in the pathogenesis of many age-related diseases. Here, we summarize the signaling pathways and cellular functions of FoxO proteins. We also review the complex role of FoxO in aging and age-related diseases, with focus on type 2 diabetes and Alzheimer’s disease and discuss the possibility of FoxO as a molecular link between aging and disease risks.