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Journal of Visualized Experiments : JoVE Jun 2023This research aims to explore the therapeutic effect and potential mechanisms of Huazhuojiedu decoction (HZJD) for alleviating precancerous lesions of gastric cancer...
This research aims to explore the therapeutic effect and potential mechanisms of Huazhuojiedu decoction (HZJD) for alleviating precancerous lesions of gastric cancer (PLGC) both in vivo and in vitro. HZJD is a traditional Chinese herbal formula consisting of 11 herbs. Sprague-Dawley (SD) rats were randomly divided into four subgroups: control group, model group, positive drug group, and HZJD group. Hematoxylin-eosin (H&E) staining, high iron diamine-alcian blue (HID-AB) staining, alcian blue-periodic acid Schiff (AB-PAS) staining, immunohistochemistry, immunofluorescence, RT-qPCR, and Western blot assays were performed after 10 weeks of HZJD treatment. In vitro, the cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation. RT-qPCR and Western blot assays were performed to evaluate mitophagy levels. The results indicated that HZJD could retard the pathological progression in PLGC rats and reduce PLGC cell proliferation. Treatment with HZJD significantly increased the mRNA and protein expression levels of Sirt3, Foxo3a, Parkin, and LC3 II/I, while decreasing the mRNA and protein expression levels of p62 and Tomm20. HZJD was found to have the ability to reverse the decline in mitophagy activity both in vivo and in vitro. In conclusion, the study assessed the impact of HZJD and provided evidence regarding its potential molecular mechanism.
Topics: Rats; Animals; Stomach Neoplasms; Rats, Sprague-Dawley; Mitophagy; Precancerous Conditions; Cell Proliferation
PubMed: 37458458
DOI: 10.3791/65271 -
American Journal of Physiology. Renal... Aug 2023Renin cells are precursors for other cell types in the kidney and show high plasticity in postnatal life in response to challenges to homeostasis. Our previous...
Renin cells are precursors for other cell types in the kidney and show high plasticity in postnatal life in response to challenges to homeostasis. Our previous single-cell RNA-sequencing studies revealed that the dual zinc-finger transcription factor , which is important for cell lineage commitment and differentiation, is expressed in mouse renin cells under normal conditions and homeostatic threats. We identified a potential Gata3-binding site upstream of the renin gene leading us to hypothesize that is essential for renin cell identity. We studied adult mice with conditional deletion of in renin cells: ; () and control Gata3; counterparts. Gata3 immunostaining revealed that mice had significantly reduced Gata3 expression in juxtaglomerular, mesangial, and smooth muscle cells, indicating a high degree of deletion of in renin lineage cells. mice exhibited a significant increase in blood urea nitrogen, suggesting hypovolemia and/or compromised renal function. By immunostaining, renin-expressing cells appeared very thin compared with their normal plump shape in control mice. Renin cells were ectopically localized to Bowman's capsule in some glomeruli, and there was aberrant expression of actin-α signals in the mesangium, interstitium, and Bowman's capsule in mice. Distal tubules showed dilated morphology with visible intraluminal casts. Under physiological threat, mice exhibited a lower increase in mRNA levels than controls. Hematoxylin-eosin, periodic acid-Schiff, and Masson's trichrome staining showed increased glomerular fusion, absent cubical epithelial cells in Bowman's capsule, intraglomerular aneurysms, and tubular dilation. In conclusion, our results indicate that is crucial to the identity of cells of the renin lineage. , a dual zinc-finger transcription factor, is responsible for the identity and localization of renin cells in the kidney. Mice with a conditional deletion of in renin lineage cells have abnormal kidneys with juxtaglomerular cells that lose their characteristic location and are misplaced outside and around arterioles and glomeruli. The fundamental role of in renin cell development offers a new model to understand how transcription factors control cell location, function, and pathology.
Topics: Mice; Animals; Renin; GATA3 Transcription Factor; Kidney; Kidney Glomerulus; Kidney Diseases; Zinc
PubMed: 37345845
DOI: 10.1152/ajprenal.00098.2023 -
Sleep Feb 2024Medication-induced central sleep apnea (CSA) is one of the 8 categories of causes of CSA but in the absence of awareness and careful history may be misclassified as...
Medication-induced central sleep apnea (CSA) is one of the 8 categories of causes of CSA but in the absence of awareness and careful history may be misclassified as primary CSA. While opioids are a well-known cause of respiratory depression and CSA, non-opioids medications including sodium oxybate, baclofen, valproic acid, gabapentin and ticagrelor are less well-recognized. Opioids-induced respiratory depression and CSA are mediated primarily by µ-opioid receptors, which are abundant in the pontomedullary centers involved in breathing. The non-opioid medications, sodium oxybate, baclofen, valproic acid and gabapentin, act upon brainstem gamma-aminobutyric acid (GABA) receptors, which co-colonize with µ-opioid receptors and mediate CSA. The pattern of ataxic breathing associated with these medications is like that induced by opioids on polysomnogram. Finally, ticagrelor also causes periodic breathing and CSA by increasing central chemosensitivity and ventilatory response to carbon dioxide. Given the potential consequences of CSA and the association between some of these medications with mortality, it is critical to recognize these adverse drug reactions, particularly because discontinuation of the offending agents has been shown to eliminate CSA.
PubMed: 38334297
DOI: 10.1093/sleep/zsae038 -
Indian Dermatology Online Journal 2023A few recent studies have shown fungal elements within the hair follicle epithelium, which may act as a reservoir and responsible for recurrent dermatophytosis.
BACKGROUND
A few recent studies have shown fungal elements within the hair follicle epithelium, which may act as a reservoir and responsible for recurrent dermatophytosis.
OBJECTIVES
To assess the clinical patterns, mycological profile, and histopathology of recurrent dermatophytosis and to determine the prevalence of fungal hyphae in the hair follicle epithelium and other appendages.
MATERIALS AND METHODS
One hundred and fifty clinically diagnosed cases of recurrent dermatophytic infection were included. Skin samples were taken for direct microscopy, fungal culture, and histopathological analysis. Haematoxylin and eosin and special staining with periodic acid Schiff (PAS) and Gomori's methenamine silver (GMS) were performed to detect the fungal hyphae in the skin and hair follicle epithelium.
RESULTS
The most common clinical pattern observed was tinea corporis et cruris in 64 patients (42.66%). On direct microscopy and fungal culture, positive results were obtained in 116 cases (77.33%) and 78 (52%) cases, respectively. Presence of fungal hyphae in the stratum corneum, hair follicle, and acrosyringium was seen in 107 patients (71.33%), 47 patients (31.33%), and five patients (3.33%), respectively. Out of the 52 cases with hair follicle and eccrine gland involvement, history of fixed drug combinations (FDC) cream use was present in 42 cases (80.76%) and absent in ten cases (19.24%) ( = 0.000062).
LIMITATIONS
Skin samples were taken only from a single skin lesion. Higher incidence of follicular invasion may have been detected if multiple biopsy samples were taken.
CONCLUSION
Hair follicle/eccrine sweat gland involvement was observed in nearly one-third of the patients, which may act as a reservoir and may be responsible for recurrence and chronicity. Histopathology should be considered as an important adjuvant tool in recurrent dermatophytosis to establish the extent of the infection, which guides the further management.
PubMed: 38099009
DOI: 10.4103/idoj.idoj_670_22 -
Nicotine & Tobacco Research : Official... Nov 2023Although the greater popularity of electronic cigarettes (EC) among asthmatics is alarming, there is limited knowledge of the long-term consequences of EC exposure in...
INTRODUCTION
Although the greater popularity of electronic cigarettes (EC) among asthmatics is alarming, there is limited knowledge of the long-term consequences of EC exposure in asthmatics.
AIMS AND METHODS
Mild asthmatic C57/BL6J adult male and female mice were established by intranasal insufflation with three combined allergens. The asthmatic and age and sex-matched' naïve mice were exposed to air, nicotine-free (propylene glycol [PG]/vegetable glycerin [VG]-only), or PG/VG+Nicotine, 4 hours daily for 3 months. The effects of EC exposure were accessed by measuring cytokines in bronchoalveolar lavage, periodic acid-schiff (PAS) staining, mitochondrial DNA copy numbers (mtCN), and the transcriptome in the lung. Significance was false discovery rate <0.2 for transcriptome and 0.05 for the others.
RESULTS
In asthmatic mice, PG/VG+Nicotine increased PAS-positive cells and IL-13 compared to mice exposed to air and PG/VG-only. In naïve mice exposed to PG/VG+Nicotine and PG/VG-only, higher INF-γ was observed compared to mice exposed only to air. PG/VG-only and PG/VG+Nicotine had significantly higher mtCN compared to air exposure in asthmatic mice, while the opposite pattern was observed in non-asthmatic naïve mice. Different gene expression patterns were profoundly found for asthmatic mice exposed to PG/VG+Nicotine compared to PG/VG-only, including genes involved in mitochondrial dysfunction, oxidative phosphorylation, and p21-activated kinase (PAK) signaling.
CONCLUSIONS
This study provides experimental evidence of the potential impact of nicotine enhancement on the long-term effects of EC in asthmatics compared to non-asthmatics.
IMPLICATIONS
The findings from this study indicate the potential impact of EC in asthmatics by addressing multiple biological markers. The long-term health outcomes of EC in the susceptible group can be instrumental in supporting policymaking and educational campaigns and informing the public, healthcare providers, and EC users about the underlying risks of EC use.
Topics: Male; Mice; Female; Animals; Nicotine; Electronic Nicotine Delivery Systems; Asthma; Lung; Propylene Glycol; Glycerol; Vegetables
PubMed: 37349133
DOI: 10.1093/ntr/ntad100 -
World Journal of Gastrointestinal... Mar 2024The Alcian blue (AB) and periodic acid Schiff (PAS) stains are representative mucus markers in gastric signet ring cell carcinoma (SRCC). They are low-cost special...
BACKGROUND
The Alcian blue (AB) and periodic acid Schiff (PAS) stains are representative mucus markers in gastric signet ring cell carcinoma (SRCC). They are low-cost special staining methods used to detect acidic mucus and neutral mucus, respectively. However, the clinical importance of the special combined AB and PAS stain is unclear.
AIM
To investigate AB expression, PAS expression and the AB-to-PAS (A/P) ratio in gastric SRCC patients and to assess patient prognosis.
METHODS
Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS, and signet ring cell positivity was assessed quantitatively. Immunohistochemical staining for Ki67, protein 53 (P53) and human epidermal growth factor receptor 2 (HER2) was performed simultaneously. The cancer-specific survival (CSS) rate was estimated Kaplan-Meier analysis. Cox proportional hazards models were used for univariate and multivariate survival analyses.
RESULTS
Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup ( < 0.001). The 3-year CSS rate in the A/P ≤ 0.5 group was significantly greater than that in the A/P > 0.5 group ( = 0.042). Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter, lymph node metastasis, vessel carcinoma embolus, tumor stage, the A/P ratio and the expression of Ki67, P53 and the PAS. Cox multivariate regression analysis confirmed that low PAS expression [hazard ratio (HR) = 3.809, 95% confidence interval (CI): 1.563-9.283, = 0.003] and large tumor diameter (HR = 2.761, 95%CI: 1.086-7.020, = 0.033) were independent risk factors for poor prognosis.
CONCLUSION
A/P > 0.5 is potentially a risk factor for prognosis, and low PAS expression is an independent risk factor in the prognosis of gastric SRCC. PAS expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.
PubMed: 38577442
DOI: 10.4251/wjgo.v16.i3.687 -
Journal of Molecular Modeling Apr 2024The electronic, discrete water solvation, and vibrational properties of zwitterionic sulfanilic acid were thoroughly investigated using periodic and non-periodic DFT...
CONTEXT
The electronic, discrete water solvation, and vibrational properties of zwitterionic sulfanilic acid were thoroughly investigated using periodic and non-periodic DFT approaches. The periodic-DFT results, obtained by employing the PBE-TS functional (Perdew-Burke-Ernzerhof (PBE) functional with the Tkatchenko and Scheffler (TS) dispersion correction) were first presented in order to analyze the band structures of the studied crystal. An attentive reading of the predicted band structures has shown three lowest gap energies calculated at 4.23, 4.24, and 4.29 eV arising from the Γ→Γ, Γ→Z, and Γ→S transitions, respectively. Then, non-periodic calculations were carried out, at the B3LYP-D3 level of theory (B3LYP functional with the D3 Grimme dispersion correction) in order to optimize the sulfanilic acid-(HO) complex. Starting from the optimized structure, non-covalent interaction calculations were performed and the H-bonding, van der Waals, and steric effect interactions were identified. Finally, the PBE-TS calculations were strengthened by conducting anharmonic B3LYP-D3 calculations in order to achieve a complete decryption of the experimental IR spectrum of sulfanilic acid. The spectral analysis is not limited only to the interpretation of both the NH/CH stretching and fingerprint regions but also extended to the 1800-2600 cm region, which is characterized by a strong anharmonic effect. In the latter wavenumber region, the large experimental IR band centered at 1937 cm is reproduced theoretically employing the anharmonic B3LYP-D3 calculations. The similarity of this band with those usually considered as a fingerprint of zwitterionic amino acids is observed, and its origin is elucidated theoretically. In the vibrational spectroscopy field, the calculations presented in this study are probably the most appropriate for achieving vast analysis and accurate assignments of vibrational spectra of hydrogen bonding compounds recorded in the solid state.
METHOD
The periodic and non-periodic calculations were conducted within the Density Functional Theory (DFT) using the Generalized Gradient Approximation (GGA) at the PBE-TS level of theory and B3LYP-D3 functional with the 6-311++G(d,p) basis set, respectively. The PBE-TS and B3LYP-D3/6-311++G(d,p) calculations were performed using the CASTEP and Gaussian 09 programs, respectively. In addition, The non-covalent interactions were calculated by the Multiwfn 3.8 software. The obtained results for different calculations were visualized by employing the visualization tools in Materials Studio, GaussView, VMD, and Gnuplot programs.
PubMed: 38570393
DOI: 10.1007/s00894-024-05911-6 -
Journal of Cancer Research and Clinical... Sep 2023Vasculogenic mimicry (VM), an alternative microvascular circulation independent of angiogenesis, is formed by aggressive cancer cells. Tumor-expressed B7-H3 has been...
BACKGROUND
Vasculogenic mimicry (VM), an alternative microvascular circulation independent of angiogenesis, is formed by aggressive cancer cells. Tumor-expressed B7-H3 has been reported to promote VM formation in hepatocellular carcinoma and modulate angiogenesis in breast cancer and colorectal cancer. However, its effects on VM generation and angiogenesis in non-small cell Lung cancer (NSCLC) remained to be elucidated.
METHODS
CRISPR/Cas9-mediated B7-H3 knockout (KO) was conducted in NSCLC A549 and H3255 cells. The expression of VM-related proteins, including vascular endothelial (VE)-cadherin and matrix metalloproteinase 14 (MMP14), and the secretion of vascular endothelial growth factor (VEGF) were measured by western blotting and chemiluminescence assay in both B7-H3 KO and mock-edited A549 and H3255 cells. To examine VM formation, a three-dimensional (3D) culture model was used for B7-H3 KO and mock A549 and H3255 cells. For in vivo analysis, xenograft mice models were established using B7-H3 KO and mock-edited A549 cells, and immunohistochemical (CD31) and histochemical (periodic acid-Schiff, PAS) double staining were performed to identify VM and endothelial vessels in tumor tissues. Finally, specific signaling inhibitors were used to analyze B7-H3-induced signaling pathway responsible for VE-cadherin and MMP14 expression and VM generation.
RESULTS
Higher expression of B7-H3 was associated with a worse prognosis and more advanced T-category in NSCLC. CRISPR/Cas9-mediated B7-H3 KO in A549 and H3255 cells led to decreased expression of VE-cadherin and MMP14; however, the secretion of VEGF by the two cell lines remained unchanged. In the 3D cell culture model, both B7-H3 KO A549 and H3255 cells showed a significant reduction in the formation of capillary-like tubular structures compared to mock-edited cells. In the in vivo xenograft model, mock-edited A549 cells formed excessive PAS CD31 VM channels, while B7-H3 KO restrained VM formation in the xenograft tumors. However, no significant differences were found in CD31 endothelial vessels between xenografts formed by B7-H3 KO and mock-edited A549 cells. Finally, we analyzed the signaling pathway responsible for B7-H3-induced VM formation and found that selective inhibition of the phosphoinositide 3-kinase(PI3K)/protein kinase B (AKT) hyperactivation by LY294002 was associated with decreased expression of MMP14 and VE-cadherin, and in vitro VM formation by both A549 and H3255 cells.
CONCLUSIONS
Tumor-expressed B7-H3 acts via PI3K/AKT signaling pathway to promote VM formation by NSCLC cells while bears no effects on angiogenesis in NSCLC.
Topics: Humans; Animals; Mice; Carcinoma, Non-Small-Cell Lung; Proto-Oncogene Proteins c-akt; Vascular Endothelial Growth Factor A; Matrix Metalloproteinase 14; Phosphatidylinositol 3-Kinases; Neovascularization, Pathologic; Lung Neoplasms; Cell Line, Tumor
PubMed: 37129607
DOI: 10.1007/s00432-023-04790-3 -
Ecotoxicology and Environmental Safety Jul 2023Ticlopidine exerts its anti-platelet effects mainly by antagonizing platelet p2y12 receptors. Previously, a few studies have shown that ticlopidine can induce liver...
Ticlopidine exerts its anti-platelet effects mainly by antagonizing platelet p2y12 receptors. Previously, a few studies have shown that ticlopidine can induce liver injury, but the exact mechanism of hepatotoxicity remains unclear. Oxidative stress, metabolic disorders, hepatocyte apoptosis, lipid peroxidation, and inflammatory responses can all lead to hepatic liver damage, which can cause hepatotoxicity. In this study, in order to deeply explore the potential molecular mechanisms of ticlopidine -induced hepatotoxicity, we used zebrafish as a model organism to comprehensively evaluate the hepatotoxicity of ticlopidine and its associated mechanism. Three days post-fertilization, zebrafish larvae were exposed to varying concentrations (1.5, 1.75 and 2 μg/mL) of ticlopidine for 72 h, in contrast, adult zebrafish were exposed exposure to 4 μg/mL of ticlopidine for 28 days. Ticlopidine-exposed zebrafish larvae showed changes in liver morphology, shortened body length, and delayed development of the swim bladder development. Liver tissues of ticlopidine-exposed zebrafish larvae and adults stained with Hematoxylin & Eosin revealed vacuolization and increased cellular interstitial spaces in liver tissues. Furthermore, using Oil Red O and periodic acid-Schiff staining methods and evaluating different metabolic enzymes of ticlopidine-exposed zebrafish larvae and adults suggested abnormal liver metabolism and liver injury in both ticlopidine-exposed zebrafish larvae and adults. Ticlopidine also significantly elevated inflammation and oxidative stress and reduced hepatocyte proliferation. During the rescue intervention using N-acetylcysteine, we observed significant improvement in ticlopidine-induced morphological changes in the liver, shortened body length, delayed swim bladder development, and proliferation of liver tissues showed significant improvement. In conclusion, ticlopidine might inhibit normal development and liver proliferation in zebrafish by upregulation of oxidative stress levels, thus leading to embryonic developmental toxicity and hepatotoxicity. In this study, we used zebrafish as a model organism to elucidate the developmental toxicity and hepatotoxicity induced by ticlopidine upregulation of oxidative stress signaling pathway in zebrafish, providing a theoretical basis for clinical application.
PubMed: 37531924
DOI: 10.1016/j.ecoenv.2023.115283 -
Membranes Aug 2023Membrane biofouling is the consequence of the deposition of microorganisms on polymer membrane surfaces. Polymeric membranes have garnered more attention for filtering... (Review)
Review
Membrane biofouling is the consequence of the deposition of microorganisms on polymer membrane surfaces. Polymeric membranes have garnered more attention for filtering and purifying water because of their ease of handling, low cost, effortless surface modification, and mechanical, chemical, and thermal properties. The sizes of the pores in the membranes enable micro- and nanofiltration, ultrafiltration, and reverse osmosis. Commonly used polymers for water filter membranes are polyvinyl chloride (PVA), polyvinylidene fluoride (PVDF), polyamide (PA), polyethylene glycol (PEG), polyethersulfone (PES), polyimide (PI), polyacrylonitrile (PAN), polyvinyl alcohol (PA), poly (methacrylic acid) (PMAA), polyaniline nanoparticles (PANI), poly (arylene ether ketone) (PAEK), polyvinylidene fluoride polysulfone (PSF), poly (ether imide) (PEI), etc. However, these polymer membranes are often susceptible to biofouling because of inorganic, organic, and microbial fouling, which deteriorates the membranes and minimizes their lives, and increases operating costs. Biofouling infection on polymer membranes is responsible for many chronic diseases in humans. This contamination cannot be eliminated by periodic pre- or post-treatment processes using biocides and other chemicals. For this reason, it is imperative to modify polymer membranes by surface treatments to enhance their efficiency and longevity. The main objective of this manuscript is to discuss application-oriented approaches to control biofouling on polymer membranes using various surface treatment methods, including nanomaterials and fouling characterizations utilizing advanced microscopy and spectroscopy techniques.
PubMed: 37623797
DOI: 10.3390/membranes13080736