Hydrogen Sulfide Attenuates Lipopolysaccharide-Induced Inflammation via the P-glycoprotein and NF-κB Pathway in Astrocytes.

Astrocyte activation is key in neurodegenerative diseases. Hydrogen sulfide (H2S) exhibits neuroprotective effects on astrocytes, although the underlying molecular mechanism remains unclear. Here, we explored the effects of H2S on lipopolysaccharide (LPS)-induced astrocyte activation and astrocyte-mediated neuroinflammation. After inducing primary astrocytes via LPS exposure, H2S levels were altered. The generation and secretion of inflammatory mediators by astrocytes and their interrelation with P-glycoprotein (P-gp), an important transporter belonging to the ABC transporter family, were assessed. Activated astrocytes showed upregulated glial fibrillary acidic protein (GFAP) mRNA expression, and significantly increased proinflammatory factor mRNA/protein expression and release. The secretory capacity of astrocytes was reduced, with significantly decreased proinflammatory factor levels in culture supernatant after P-gp inhibitor verapamil pretreatment. The increase in the intracellular H2S level inhibited LPS-induced GFAP expression and P65 nuclear entry in astrocytes. mRNA expression and release of proinflammatory factors were reduced significantly, with no significant changes in cytoplasmic protein expression. S-sulfhydration levels increased significantly with the increased concentration of sodium hydrosulfide or S-adenosyl-L-methionine addition, with only moderate changes in astrocyte P-gp expression. H2S regulates NF-κB activation, leads to S-sulfhydration of P-gp, and inhibits the biosynthesis and secretion of proinflammatory factors by astrocytes. The regulatory effects of H2S on astrocytes may have clinical value for exploring new therapeutic strategies against neurodegenerative diseases.

Psittacosis caused severe community-acquired pneumonia accompanied by acute hypoxic respiratory failure: a multicenter retrospective cohort study from China.

INTRODUCTION: Psittacosis can cause severe community-acquired pneumonia (CAP). The clinical manifestations of psittacosis range from subclinical to fulminant psittacosis with multi-organ failure. It is essential to summarize the clinical characteristic of patients with severe psittacosis accompanied by acute hypoxic respiratory failure (AHRF). METHODS: This retrospective study included patients with severe psittacosis caused CAP accompanied by AHRF from 19 tertiary hospitals of China. We recorded the clinical data, antimicrobial therapy, respiratory support, complications, and outcomes. Chlamydia psittaci was detected on the basis of metagenomic next-generation sequencing performed on bronchoalveolar lavage fluid samples. Patient outcomes were compared between the treatment methods. RESULTS: This study included 45 patients with severe CAP and AHRF caused by psittacosis from April 2018 to May 2021. The highest incidence of these infections was between September and April. There was a history of poultry contact in 64.4% of the patients. The median PaO2/FiO2 of the patients was 119.8 (interquartile range, 73.2 to 183.6) mmHg. Four of 45 patients (8.9%) died in the ICU, and the median ICU duration was 12 days (interquartile range, 8 to 21) days. There were no significant differences between patients treated with fluoroquinolone initially and continued after the diagnosis, fluoroquinolone initially followed by tetracycline, and fluoroquinolone combined with tetracycline. CONCLUSION: Psittacosis caused severe CAP seems not rare, especially in the patients with the history of exposure to poultry or birds. Empirical treatment that covers atypical pathogens may benefit such patients, which fluoroquinolones might be considered as an alternative.

Association of Dietary Patterns with Parkinson's Disease: A Cross-Sectional Study Based on the United States National Health and Nutritional Examination Survey Database.

INTRODUCTION: Although studies have explored some dietary patterns for Parkinson's disease (PD), more other dietary patterns and food item under the dietary pattern are needed to investigate. This study aimed to identify more categories of dietary patterns for PD and further explore the association of single food item with PD. METHODS: The 2015-2018 US National Health and Nutritional Examination Survey (NHANES) database was used for data extraction. The data on demographics and nutrient intake were collected. Dietary patterns were derived from food categories by factor analysis. The association between dietary patterns or single food item and PD was explored using logistic regression analysis in the overall and only in secure PD cases, and results were expressed as odds ratio (OR) with 95% confidence intervals (CIs). Sensitivity analysis was performed by excluding participants using unsecure PD medication. RESULTS: Among 5,824 participants aged over 50 years, 91 were diagnosed as PD. Factor analysis identified 5 major dietary pattern factors. We observed that the increased adherence to Mediterranean diet (MeDi) was associated with the reduced odds of PD (OR = 0.78, 95% CI: 0.65-0.93). The higher adherence to Western pattern was associated with the increased odds of PD (OR = 2.19, 95% CI: 1.16-4.14). In addition, high intake of sweets under Western pattern was found to be associated with the higher odds of PD (OR = 2.01, 95% CI: 1.08-3.71). CONCLUSIONS: The odds of PD decreased by higher MeDi adherence and increased by higher Western pattern adherence, especially sweets intake in this pattern, suggesting population ≥50 years should adhere to MeDi pattern and decrease the adherence to Western pattern, reducing the intake of sweets.

Dietary supplementation with probiotics increases growth performance, improves the intestinal mucosal barrier and activates the Wnt/ß-catenin pathway activity in chicks.

BACKGROUND: Probiotics comprise effective feed additives that can replace antibiotics in animal livestock production. However, mono-strain probiotics appear less effective because of their instability. Therefore, the present study aimed to investigate dietary supplementation with compound probiotics (CPP) on growth performance, diarrhea rate and intestinal mucosal barrier, as well as the possible molecular mechanism, in chicks. In total, 360 1-day-old chicks of the Hy-Line Brown Chicks were randomly divided into the control group (CON, basal diet), chlortetracycline group (500 mg kg-1 CTC) and compound probiotics group (1000 mg kg-1 CPP, consisting of Bacillus subtilis, Bacillus licheniformis, Enterococcus faecium and yeast). The experiment period was 56 days. RESULTS: The results showed that, in comparison with the CON group, CPP significantly increased the average daily feed intake and average daily gain of chicks and reduced diarrhea (P < 0.05). The probiotic group exhibited increased immune organ (i.e. spleen and thymus) mass and increased levels of serum immunoglobulin (Ig)A, IgM and IgG (P < 0.05) compared to the CTC group. In addition, the jejunal mass and morphology were improved in the probiotic group (P < 0.05). Moreover, CPP reinforced jejunal barrier function, as indicated by increased transepithelial electrical resistance, protein expression of occludin and claudin-1, and diamine oxidase levels in the jejunum (P < 0.05). Likewise, enhanced fluorescence signals of proliferating cell nuclear antigen-labeled mitotic cells and villin-labeled absorptive cells in the jejunum (P < 0.05) suggested that CPP promoted intestinal stem cells activity. Mechanistically, the Wnt/ß-catenin signaling pathway, including ß-catenin, TCF4, c-Myc, cyclin D1 and Lgr5, was amplified in the jejunum by CPP addition (P < 0.05). CONCLUSION: The present study demonstrated that dietary supplementation with CPP reinforced the jejunal epithelial integrity by activating Wnt/ß-catenin signaling and enhanced immune function in chicks. © 2023 Society of Chemical Industry.

Response of grafting tobacco to low potassium stress.

BACKGROUND: In the previous study, we investigated the alleviation effect of grafting on potassium uptake in roots and tobacco growth inhibition under low potassium stress. However, the effect of grafting on the low potassium stress perception and coping mechanism of tobacco at the whole plant level is not clear now. In order to clearly understand the impact of grafting on potassium deficit responding mechanism in tobacco, a mutual grafting experiment has been conducted in two varieties of tobacco ('Wufeng No.2' and 'Yunyan 87') in different K supply level (5 mmol L- 1 and 0.5 mmol L- 1 K). RESULTS: The results show that compared with the self-rooted seedlings, grafting significantly increased the potassium content of the whole plant of Yunyan 87 (97.57 and 189.74% under normal potassium and low potassium conditions, respectively), and the increase in shoots was greater. The data of whole plant K content distribution and tobacco hypocotyls net K+ flux demonstrates that potassium stress makes plants more inclined to maintain K+ in the shoot rather than root. In addition, when K deficiency occurs, grafting could reduce the time required for downward net K+ flux in tobacco hypocotyl to decrease to stable levels. The results of net K+ flux in the roots indicated that K channel proteins and transporters play different roles in two rootstocks in terms of potassium tolerance. Transcription level analysis suggested that the increased circulating efficiency of K+ between the shoots and roots in tobacco constitutes one means to low potassium stress adaptation. CONCLUSIONS: Grafting can activate more K+ channels in tobacco 'Yunyan 87', this means a more active K+ cycle, higher potassium content in shoot and faster response to low potassium stress signals in grafting tobacco. In addition, grafting can also change the K+ absorption mode of tobacco root from being dominated by HATS to being jointly responsible by HATS and LATS, greatly improving the ability of K+ transmembrane transportation on root surface under low potassium stress. These are undoubtedly the reasons why grafting tobacco performs better in coping with low potassium stress.

Recurrent Talaromyces marneffei Infection Presenting with Intestinal Obstruction in a Patient with Systemic Lupus Erythematosus.

Talaromyces marneffei is an important opportunistic pathogen mainly afflicting the HIV-infected patients, in rare instance, it could cause infection in non-HIV-infected individuals. We report a 51-year-old Chinese woman who, with histories of SLE for 14 years and disseminated talaromycosis for 4 years, occurred partial intestinal obstruction that was demonstrated to be caused by Talaromyces marneffei infection. The randomly amplified polymorphic DNA results of paraffin-embedded tissues from both the present episode and the previous infection suggested that the present infection was a recurrent. The patient was performed excision of involved intestine and treated with oral itraconazole at a daily dose of 400 mg for 3 months, leading to an excellent response. However, she died with unknown reason more than a year later. We also reviewed the literature on Talaromyces marneffei infection associated with SLE as well as intestinal talaromycosis alone.

Grafting alleviates potassium stress and improves growth in tobacco.

BACKGROUND: Potassium is a nutrient element necessary for tobacco growth. Tobacco leaves with high potassium content are elastic and tough, rich in oil. And the same time, potassium can also improve the scent and aromatic value of flue-cured tobacco by regulating the synthesis of aromatic hydrocarbons in leaves.. It is an important quality indicator for flue-cured tobacco. However, the potassium concentration in tobacco leaves in most areas of China is generally lower than the global standard for high quality tobacco. Two tobacco genotypes were grafted to each other under different potassium levels to test whether potassium content and plant growth can be improved by grafting in tobacco. RESULTS: The growth of tobacco in all treatments was inhibited under potassium starvation, and grafting significantly alleviated this potassium stress in 'Yunyan 87'. The trends in whole plant K+ uptake and K+ transfer efficiency to the leaves corresponded to the growth results of the different grafts. The nutrient depletion test results showed that the roots of 'Wufeng No.2' had higher K+ absorption potential, K+ affinity, and K+ inward flow rate. K+ enrichment circles appeared at the endoderm of the root section in the energy dispersive X-ray figure, indicating that the formation of Casparian strips may be partly responsible for the lower rate of lateral movement of K+ in the roots of 'Yunyan 87'. Gene expression analysis suggested that energy redistribution at the whole plant level might constitute one strategy for coping with potassium starvation. The feedback regulation effects between scion 'Wufeng No.2' and rootstock 'Yunyan 87' indicated that the transmission of certain signaling substances had occurred during grafting. CONCLUSIONS: 'Wufeng No.2' tobacco rootstock grafting can increase the K+ uptake and transport efficiency of 'Yunyan 87' and enhance plant growth under potassium stress. The physiological mechanism of the improved performance of grafted tobacco is related to higher K+ uptake and utilization ability, improved xylem K+ loading capacity, and up-regulated expression of genes related to energy supply systems.

Pregnane X Receptor Not Nuclear Factor-kappa B Up-regulates P-glycoprotein Expression in the Brain of Chronic Epileptic Rats Induced by Kainic Acid.

Drug-resistance epilepsy (DRE) is attributed to the brain P-glycoprotein (P-gp) overexpression. We previously reported that nuclear factor-kappa B (NF-κB) played a critical role in regulating P-gp expression at the brain of the acute seizure rats. This study was extended further to investigate the interaction effect of NF-κB and pregnane X receptor (PXR) on P-gp expression at the brain of chronic epileptic rats treated with carbamazepine (CBZ). The chronic epileptic models were induced by the micro-injection of kainic acid (KA) into rats' hippocampus. Subsequently, the successful models were treated with different intervention agents of CBZ; PMA(a non-specific PXR activity inhibitor) or PDTC(a specific NF-κB activity inhibitor) respectively. The expression levels of P-gp and its encoded gene mdr1a/b were significantly up-regulated on the brain of KA-induced chronic epilepsy rats or the epilepsy rats treated with CBZ for 1 week, meanwhile with a high expression of PXR. The treatment of PMA dramatically reduced both PXR and P-gp expressions at the protein and mRNA levels in the chronic epilepsy brain. By compared to the epilepsy model group, the P-gp expression was not markedly attenuated by the inhibition of NF-κB activity with PDTC treatment, nevertheless with a decrease of NF-κB expression in this intervention group. Higher levels of proinflammatory cytokines(IL-1ß, IL-6, TNF-α) were found both in the brain tissue and the serum in the epilepsy rats of each group. There was a declined trend of the pro-inflammatory cytokines expression of the PDTC treatment group but with no statistical significance. This study demonstrates for the first time that P-gp up-regulation is due to increase PXR expression in the chronic phase of epilepsy, differently from that NF-κB signaling may induce the P-gp expression in the acute seizure phase. Our results offer insights into the mechanism underlying the development of DRE using or not using CBZ treatment.

Acetazolamide Suppresses Multi-Drug Resistance-Related Protein 1 and P-Glycoprotein Expression by Inhibiting Aquaporins Expression in a Mesial Temporal Epilepsy Rat Model.

BACKGROUND Mesial temporal epilepsy (MTLE) is the most common type of focal epilepsy in adults, and is often drug-resistant. This study investigated the effects of aquaporins (AQP) inhibitor on multi-drug-resistant protein expression in an MTLE rat model. MATERIAL AND METHODS The MTLE rat model was established by injecting pilocarpine into rats. The MTLE rats were divided into an MTLE-6 h group, an MTLE-12 h group, and an MTLE-24 h group, together with a normal saline group (NS), to examine the AQP4 expression by using Western blot assay and immunohistochemistry assay. The other 18 MTLE model rats were used to observe the effects of the AQP4 inhibitor, acetazolamide, on the multi-drug-resistant protein 1 (MRP1) and P-glycoprotein (Pgp) by using Western blot and immunohistochemistry assays, respectively. RESULTS AQP4 expression was enhanced in hippocampal tissues of MTLE model rats compared to NS rats (P<0.05). More positively stained AQP4 was discovered in hippocampal tissues of MTLE model rats. AQP4 inhibitor significantly decreased multi-drug-resistant protein MRP1 and Pgp expression in the AQP4 inhibitor Interfere group and the AQP4 inhibitor Therapy group compared to the TMLE model group (P<0.05). CONCLUSIONS The present findings confirm that the AQP4 inhibitor, acetazolamide, effectively inhibits the multi-drug-resistant protein, MRP1, and Pgp, in the MTLE rat model.

Aquagenic cutaneous disorders.

Aquagenic cutaneous disorders, which include aquagenic urticaria, aquagenic pruritus, and aquagenic acrokeratoderma, are a group of rare diseases characterized by skin lesions or discomfort induced by brief contact with water. Aquagenic urticaria is characterized by pruritic wheals that occur at the sites of water contact, either immediately or within minutes, and disappear within 30-60 min after water removal. Aquagenic pruritus presents with severe pruritus or a stinging, tingling, or burning sensation without any visible skin changes. These symptoms occur immediately or within minutes after the skin is exposed to water, lasting for one hour or longer. Aquagenic acrokeratoderma usually presents with whitish papules and plaques, edema, and hyperwrinkling within 2-20 min after brief exposure to water; symptoms disappear within minutes to one hour after drying. The pathomechanisms of these diseases are not yet fully understood, and their diagnosis is primarily based on clinical features. Treatment remains a challenge. Herein, we review the literature regarding these unusual disorders.

Hybrid eccrine gland and hair follicle hamartoma: a new entity of adnexal nevus.

Eccrine nevus shows increase in number or size of eccrine glands, whereas hair follicle nevus is composed of densely packed normal vellus hairs, and eccrine-pilar angiomatous nevus reveals increase of eccrine, pilar, and angiomatous structures. No case with increased number of both eccrine glands and hair follicles only in the dermis has been previously reported. A 10-month-old girl presented with cutaneous hamartoma with overlying skin hyperpigmentation on her left hypochondrium since 3 months of age, in whom the lesion was completely excised. Histopathology demonstrated evidently increased number of both eccrine glands and hair follicles in the dermis with reactive hyperplasia of collagen fibers. No recurrence occurred after the tumor was completely excised. A term "hybrid eccrine gland and hair follicle hamartoma" is proposed for this unique lesion.

Recurrent facial erythema with burning sensation and increased temperature: a variant of erythromelalgia or a new entity?

OBJECTIVE: Erythromelalgia is a rare clinical syndrome characterized by episodic attacks of burning pain, erythema, and increased temperature, primarily affecting the extremities, and in rare instances, involving the ear, face, neck, and the scrotum. The dermatoscopic features of erythromelalgia in a case with solely facial involvement have never been described previously. OBSERVATIONS: We describe a 14-year-old female who presented with erythema, burning sensation, and warmth on her face only, which mimic the features of erythromelalgia. Physical examination showed higher temperature on the involved cheeks than on axillas during the episode, while the temperature on both areas was the same between episodes. Dermatoscope showed more dilated vessels inside the erythema during the episodes than between the episodes. The symptoms had excellent response to the combination treatment of gabapentin, indomethacin, and topical lidocaine compounds. CONCLUSIONS: The present case is considered to be a variant of erythromelalgia. Its erythema may be resulted from the dilated vessels. Combination of modalities may provide effective management for erythromelalgia. "Erythermalgia" may be better than "erythromelalgia" to describe such conditions.

Mandibuloacral dysplasia type A-associated progeria caused by homozygous LMNA mutation in a family from Southern China.

BACKGROUND: Mandibuloacral dysplasia type A (MADA) is a rare autosomal recessive disorder, characterized by growth retardation, skeletal abnormality with progressive osteolysis of the distal phalanges and clavicles, craniofacial anomalies with mandibular hypoplasia, lipodystrophy and mottled cutaneous pigmentation. Some patients may show progeroid features. MADA with partial lipodystrophy, more marked acral, can be caused by homozygous or compound heterozygous mutation in the gene encoding lamin A and lamin C (LMNA). MADA and Hutchinson-Gilford progeria syndrome are caused by the same gene and may represent a single disorder with varying degrees of severity. MAD patients characterized by generalized lipodystrophy (type B) affecting the face as well as extremities and severe progressive glomerulopathy present heterozygous compound mutations in the ZMPSTE24 gene. CASES PRESENTATIONS: We described a rare pedigree from Southern China, among them all three children presented with phenotypes of MADA associated progeria. The two elder sisters had developed severe mandibular hypoplasia associated progeria since the age of 1 year. The eldest sister showed a progressive osteolysis. The youngest son of 10 months showed severer lesions than those of his sisters at the same age, and presented possible muscle damage, and his symptoms progressed gradually. Three genes mutations including LMNA, ZMPSTE24 and BANF1 were tested in the family. LMNA gene sequencing revealed a homozygous missense mutation, c.1579C > T, p.R527C for all three siblings, and heterozygous mutations for their parents, whereas no mutations of ZMPSTE24 and BANF1 genes was detected among them. CONCLUSIONS: The same homozygous mutation of c.1579C > T of LMNA gene led to MADA associated progeria for the present family. The course of osteolysis for MADA is progressive.

Erythema associated with pain and warmth on face and ears: a variant of erythermalgia or red ear syndrome?

Erythermalgia is a rare cutaneous disorder characterized by attacking of erythema, pain and increased temperature, which primarily involves the extremities and may infrequently extend to the neck, face, ears and even the scrotum. We reported an 18-year-old woman who presented with 3 years history of sole involvement of attacking erythema, pain and warmth over her face and ears without any other associations. The frequency and severity of the flares progressed gradually during the course. Cutaneous examination revealed erythema, increased temperature and tenderness on the face and ears during the flare. The symptoms could be relieved rapidly by cooling. Dermatoscope showed that vessels inside the erythema were more dilated during the episode than after application of ice. The lesion is considered a rare variant of erythermalgia with sole involvement of face and ears. The symptoms had mild response to oral antihistamines, topical steroids and tacrolimus, but had excellent response to the combinative therapy of aspirin and paroxetins.