UVB irradiation induces pro-inflammatory cytokines including interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα) in the skin. TNFα stimulates the chemotaxis of inflammatory cells to the skin. ...These cells secrete metalloproteinases (MMPs) and other enzymes that damage the cutaneous matrix. Therefore, blocking TNFα activity could be effective in preventing the influx of inflammatory cells and subsequent collagen degradation in the skin. In addition, TNFα downregulates procollagen mRNA, and thus blockade may be beneficial to production of type I collagen. Female C57BL/6 J mice were treated with etanercept (TNFα blocker, 4 mg/kg/day) for 4 days 1 h prior to UVB irradiation (100 mJ/cm2/day for 5 days). On the 5th day mice were sacrificed 3 h after UVB exposure. Blocking TNFα significantly inhibited UVB-induced recruitment of macrophages, mast cells, and neutrophils. UVB-irradiated mice skin contained more mature collagen compared to etanercept and UVB + etanercept-treated mice. Skin from UVB + etanercept-treated mice had more collagen fragments relative to UVB-irradiated mice. Procollagen protein was lower in UVB-irradiated and UVB + etanercept-treated mice. TNFα blockade decreased decorin and TGF-β1 in UVB-irradiated mice compared to UVB alone. MMP13 was inhibited by etanercept in UVB-irradiated mice (p < 0.01). In conclusion, blockade of TNFα significantly decreased mature collagen in UVB-irradiated mice, while increasing collagen fragmentation and decreasing procollagen.
•Blockade of TNF-α by Etanercept largely inhibits UVB-induced inflammatory cells in the dermis.•In UVB-irradiated mice, blockade of TNFα caused large decreases in mature collagen, decorin, and TGF-β in skin.•Blockade of TNFα increased collagen fragmentation in UVB-irradiated mice, while decreasing procollagen synthesis.
Centrosome overduplication promotes mitotic abnormalities, invasion and tumorigenesis. Cells regulate the number of centrosomes by limiting centriole duplication to once per cell cycle. The ...orthogonal orientation between a mother and a daughter centriole, established at the time of centriole duplication, is thought to block further duplication of the mother centriole. Loss of orthogonal orientation (disengagement) between two centrioles during anaphase is considered a licensing event for the next round of centriole duplication. Disengagement requires the activity of Polo-like kinase 1 (Plk1), but how Plk1 drives this process is not clear. Here we employ correlative live/electron microscopy and demonstrate that Plk1 induces maturation and distancing of the daughter centriole, allowing reduplication of the mother centriole even if the original daughter centriole is still orthogonal to it. We find that mother centrioles can undergo reduplication when original daughter centrioles are only ∼80 nm apart, which is the distance centrioles normally reach during prophase.
It is well established that human tumors overproduce plasmin a serine protease that is known to promote angiogenesis, tumor growth and metastasis. However, the mechanism by which endothelial or tumor ...cells regulate the proteolytic activity of plasmin is not well understood. Cell surface receptors regulate activation of plasminogen to plasmin and its proteolytic activity. Annexin II is one of the well studied receptors for plasminogen and tPA, which binds to plasminogen and converts it to plasmin. Plasmin is a highly reactive enzyme which is physiologically involved in fibrinolysis. Since the proteolytic activity of plasmin is very tightly regulated, uncontrolled production of plasmin can degrade extracellular matrix (ECM) and basement membrane (BM) of the surrounding blood vessels. Thus plasmin plays an important role in neoangiogenesis and cancer invasion and metastasis. Therefore, the receptor which regulates plasmin generation may be an attractive target for the development of anti-cancer/anti-metastatic agents. Angiostatin (AS), internal fragment of plasminogen, has been reported to inhibit human tumor growth and metastasis. We have shown that AS binds to endothelial/cancer cell surface annexin II with high affinity and interferes with plasmin generation suggesting that the role of plasmin/plasminogen system may be more complex than we previously thought. In this review we provide a comprehensive analysis of the literature in context of the role of annexin II in angiogenesis, tumor progression and metastasis. Compelling evidence from the literature and our own findings suggest that annexin II may be a potential target for the development of effective therapeutic strategies for the treatment of cancer and its induced metastasis.
•Greywater from a middle-class Indian home was analyzed continuously for six months.•Laundry and kitchen together generated most of the BOD and COD loads.•Most of the pathogen contamination was ...contributed by bathroom/showers.•Electrocoagulation at 12V with aluminum plates effectively removed contaminants.•COD removal efficiency increased with current density but remained limited to 70%.
Wastewater produced from all the domestic uses of water sans toilet flushing is known as greywater. It is often the major component in the domestic wastewater but has fewer pollutant load. Recycling and reuse of treated greywater for non-potable purposes may significantly reduce the stress on the fresh water requirement. This article presents the result of a study undertaken for characterization as well as laboratory-based investigation for treatment of greywater generated from an Indian single household. The greywater constituted at least 80% of the total wastewater with maximum contribution (44%) from the kitchen. The treatment studies, undertaken in an electrochemical reactor where the voltage and current were varied for sacrificial aluminum anodes, revealed that about 70% of the total COD and more than 99.9% pathogens could be removed with an energy consumption of 0.3kWh/m3 of wastewater. COD removal reached a maximum of 70%, irrespective of the applied voltage and current density, at an aluminum release from the anode at a rate of 15mg/L as aluminum. The electrochemical reactor aluminum electrodes, operated with maximum potential difference of 12V, showed potential for scale-up for real-life use in households for removal of pathogens, turbidity and COD contents of greywater.
Objective
The pathogenesis of cutaneous lupus erythematosus (CLE) is multifactorial, and CLE is difficult to treat due to the heterogeneity of inflammatory processes among patients. Antimalarials ...such as hydroxychloroquine (HCQ) and quinacrine (QC) have long been used as first‐line systemic therapy; however, many patients do not respond to treatment with antimalarials and require systemic immunosuppressants that produce undesirable side effects. Given the complexity and the unpredictability of responses to antimalarial treatments in CLE patients, we sought to characterize the immunologic profile of patients with CLE stratified by subsequent treatment outcomes to identify potential biomarkers of inducible response.
Methods
We performed mass cytometry imaging of multiple immune cell types and inflammation markers in treatment‐naive skin biopsy samples from 48 patients with CLE to identify baseline immunophenotypes that may predict the response to antimalarial therapy. Patients were stratified according to their response to treatment with antimalarials, as HCQ responders, QC responders, or nonresponders.
Results
HCQ responders demonstrated increased CD4+ T cells compared to the QC responder group. Patients in the nonresponder group were found to have decreased Treg cells compared to QC responders and increased central memory T cells compared to HCQ responders. QC responders expressed increased phosphorylated stimulator of interferon genes (pSTING) and interferon‐κ (IFNκ) compared to HCQ responders. Phosphorylated STING and IFNκ were found to be localized to conventional dendritic cells (cDCs), and the intensity of pSTING and IFNκ staining was positively correlated with the number of cDCs on a tissue and cellular level. Neighborhood analysis revealed decreased regulatory cell interactions in nonresponder patients. Hierarchical clustering revealed that nonresponder patients could be further differentiated based on expression of pSTAT2, pSTAT3, pSTAT4, pSTAT5, phosphorylated interferon regulatory factor 3 (pIRF3), granzyme B, pJAK2, interleukin‐4 (IL‐4), IL‐17, and IFNγ.
Conclusion
These findings indicate differential immune cell compositions between patients with CLE, offering guidance for future research on precision‐based medicine and treatment response.
•Volumetric and acoustic properties determination of D-maltose monohydrate and D-lactose monohydratein aqueous solution of trisodium citrate (TSC).•Determination of hydration number.•Positive values ...of VoΦ,tr,KoΦ,s,trshows the supremacy of ionic-hydrophilic and hydrophilic-hydrophilic interactions.•Hepler's thermodynamic relation shows structure making and breaking behavior of of D-maltose monohydrate and D-lactose monohydrate respectively.
From the measurements of density, (ρ) and speed of sound, (u), the intermolecular interactions of D-maltose monohydrate and D-lactose monohydrate with trisodium citrate (TSC) have been explored in aqueous medium at temperatures, T = (293.15–313.15) K, pressure p = 0.1 MPa. From the experimental density measurements, apparent molar volume (VΦ), limiting apparent molar volume (VoΦ) and limiting apparent molar volume of transfer (VoΦ,tr) have been determined for various solutions of maltose and lactose in aqueous TSC. In addition, using experimental speed of sound data, apparent molar isentropic compressibility (KΦ,s), limiting apparent molar isentropic compressibility (KoΦ,s) and partial molar isentropic compression of transfer (KoΦ,s,tr) have been calculated.Further, apparent molar expansibility (EoΦ), Hepler's constant values(∂EoΦ∂T)Pand hydration number (nH)have been assessed to contribute the interpretations received from the acoustic and analysis. The assessed outcomes were construed in terms of diverse intermolecular interactions present in the ternary systems (saccharides+ water + TSC) through a co-sphere overlap model. From the Hepler's constant structure breaking nature of the solute have been confirmed.
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Abstract Background: Teenage pregnancy and motherhood are one of the global public health problems. In India, 6.8% of women aged 15–19 years began childbearing between 2019 and 2021 and this is more ...common in rural areas and socioeconomically disadvantaged states. During the National Family Health Survey-5, it was seen that 4.2% of 15–19 years were already pregnant or had children. Thus, this study aims to explore the various challenges faced by teenage mothers with the barriers in service delivery and solutions to tackling the issue from their perspective. Materials and Methods: A qualitative study with a phenomenological approach was conducted from October to November’ 2023 in the tribal hamlets of Udaipur, Rajasthan. In-depth interviews of 21 purposively selected with snowball sampling teenage mothers were conducted. Audio recording and note-taking were done during the interview. Thematic analysis was done. Results: The teenage mothers were subjected to various types of medical problems, lack of unawareness, lack of parental and spousal support, as well as psychosocial stressors and social constraints as the major challenges being faced. The major themes for its solutions were parental and spousal cooperation, education, and ownership taken by the village head. Conclusion: Lack of unawareness, medical problems, and familial issues probably due to socioeconomic factors are the major challenges for teenage mothers, whereas the prime solution, as suggested, is parental support and cooperation. Regulation on the sale of alcohol was also cited as a factor in curbing the problems of teenage pregnancy.
UVB irradiation potently induces cytokines in the skin, including IL-1α and tumor necrosis factor-α (TNF-α). The mechanism for TNF-α induction in UVB-irradiated keratinocytes is not clear. In this ...study, we explored the effects of UVB and cytokines, alone or in combination in human keratinocytes. Keratinocytes were sham- or UVB-irradiated with 30mJcm−2, and then incubated in the absence or presence of IFN-α2b, TNF-α, or IL-1α. UVB and IL-1α treatment synergistically enhanced TNF-α secretion and mRNA levels in human keratinocytes, similar to the findings reported previously in human fibroblasts. Exogenous recombinant TNF-α up-regulates its own mRNA level. However, addition of IFN-α2b did not show any additive effect on TNF-α mRNA induction. To understand the regulation of TNF-α mRNA by UVB, with or without IL-1α, we examined the transcription rate and half-life of TNF-α mRNA. Treatment of keratinocytes with IL-1α or UVB alone increased TNF-α gene transcription 4- to 5-fold over sham treatment, and TNF-α gene transcription increased 11-fold in cells treated with UVB plus IL-1α over sham. UVB with IL-1α did not enhance the half-life of TNF-α mRNA over that seen with UVB alone. In conclusion, TNF-α expression in primary keratinocytes is upregulated transcriptionally by UVB and IL-1α.
Many advanced human tumors including breast cancer overproduce plasmin that is known to promote angiogenesis and metastasis. The mechanism of this effect is poorly understood. Here we report that ...annexin II, an endothelial co-receptor for tPA (tissue-type plasminogen activator) and plasminogen, was undetectable in normal and hyperplastic ductal epithelial cells and ductal complexes. By contrast, it was consistently expressed in invasive breast cancer and ductal carcinoma in situ (DCIS) indicating its involvement in breast cancer. Using the well established invasive/metastatic MDA-MB231 cell line and the noninvasive/nonmetastatic MCF-7 human breast cancer cell line, we investigated the mechanism by which annexin II regulates breast cancer progression and metastasis. Western and Northern blot analyses demonstrate selective expression of annexin II in MDA-MB231 cells but not in poorly invasive MCF-7 cells suggesting its participation in invasive breast cancer. Since annexin II is a receptor for plasminogen, we tested whether MDA-MB231 cells are capable of producing plasmin in vitro. MDA-MB231 cell membranes induced plasmin generation in a time-dependent manner while those from MCF-7 cells failed to convert plasminogen to plasmin. The generated plasmin is capable of degrading ECM consequently facilitating cell invasion and migration, biological functions required for angiogenesis and metastasis. Plasmin generation and its dependent invasion and migration can be blocked by a monoclonal antibody to annexin II or angiostatin, potent inhibitors of angiogenesis, breast cancer, and metastasis. Our findings indicate that annexin II-dependent localized plasmin generation by human breast cancer cells could contribute to angiogenesis and metastasis. These results suggest that annexin II may be an attractive target for new anti-angiogenic and anti-breast cancer therapies.
From the density (ρ) and speed-of-sound (u) measurements, the interactions of the drug diphenhydramine-hydrochloride (DPH) with three imidazolium-based ionic liquids (ILs) ...(1-butyl-3-methylimidazolium chloride, C4mimCl, 1-hexyl-3-methylimidazolium chloride1, C6mimCl, and 1-methyl-3-octylimidazolium chloride, C8mimCl) have been investigated in aqueous medium at T = 293.15–313.15 K and experimental pressure p = 0.1 MPa. From the density calculations, the apparent molar volume (V ϕ) and the apparent partial molar volumes of transfer (Δ t V ϕ o) have been determined for various solutions of DPH in aqueous solutions of different ILs. In addition, from the speed-of-sound data, the apparent molar isentropic compressibility (K ϕ), apparent partial molar isentropic compressibility (K ϕ o), and apparent partial molar isentropic compressibility of transfer (Δ tKϕ ο ) have been calculated. The pair and triplet interaction coefficients are derived from apparent partial molar volumes of transfer. For the present mixtures, the absorption spectra have been also recorded using a UV–visible spectrophotometer. Using Hepler’s constant, the structure-making nature of the solute has been confirmed. All these calculated parameters provide detailed insights into various physicochemical interactions prevailing in the ternary system and confirm the presence of a strong attractive interaction between DPH and ILs.
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