Immunopathogenesis of urticaria: a clinical perspective on histamine and cytokine involvement.

BACKGROUND: Urticaria is a clinical condition characterized by the appearance of wheals (hives), angioedema, or both. Over the last several decades, a better understanding of the mechanisms at play in the immunopathogenesis of urticaria has underscored the existence of numerous urticaria subtypes. Separating the different kinds of urticaria explicitly helps find the best detection method for the management of this skin disorder. Subtypes of urticaria also include both spontaneous and physical types. The conventional ones include spontaneous urticaria, constituting both acute and chronic urticaria. Therefore, a broad and effective therapy is essential for the diagnosis and treatment of urticaria. METHODS: To understand the immunopathogenesis of urticaria, various databases, including PubMed, Scopus, and Web of Science, were used to retrieve original articles and reviews related to urticaria. While information on several clinical trials were obtained from clinicaltrials.gov database. RESULTS: This article highlights the immunopathogenesis involved in the intricate interaction between cellular infiltration, immune reactions, coagulation cascades, and autoantibodies that underlie urticaria's pathophysiology. CONCLUSION: The recent progress in understanding urticaria can help to understand the intricate characteristics in the immunopathogenesis of urticaria and could play a beneficial role in the management of urticaria.

Bioprotective Role of Phytocompounds Against the Pathogenesis of Non-alcoholic Fatty Liver Disease to Non-alcoholic Steatohepatitis: Unravelling Underlying Molecular Mechanisms.

Non-alcoholic fatty liver disease (NAFLD), with a global prevalence of 25%, continues to escalate, creating noteworthy concerns towards the global health burden. NAFLD causes triglycerides and free fatty acids to build up in the liver. The excessive fat build-up causes inflammation and damages the healthy hepatocytes, leading to non-alcoholic steatohepatitis (NASH). Dietary habits, obesity, insulin resistance, type 2 diabetes, and dyslipidemia influence NAFLD progression. The disease burden is complicated due to the paucity of therapeutic interventions. Obeticholic acid is the only approved therapeutic agent for NAFLD. With more scientific enterprise being directed towards the understanding of the underlying mechanisms of NAFLD, novel targets like lipid synthase, farnesoid X receptor signalling, peroxisome proliferator-activated receptors associated with inflammatory signalling, and hepatocellular injury have played a crucial role in the progression of NAFLD to NASH. Phytocompounds have shown promising results in modulating hepatic lipid metabolism and de novo lipogenesis, suggesting their possible role in managing NAFLD. This review discusses the ameliorative role of different classes of phytochemicals with molecular mechanisms in different cell lines and established animal models. These compounds may lead to the development of novel therapeutic strategies for NAFLD progression to NASH. This review also deliberates on phytomolecules undergoing clinical trials for effective management of NAFLD.

Evaluation of cilnidipine-loaded self-micro-emulsifying drug delivery system (SMEDDS) by quantification of comparative pharmacokinetic parameters using validated LC-ESI-MS/MS bioanalytical method and pharmacodynamic assessment.

OBJECTIVE: Regardless of having desired therapeutic properties many of the recently approved drugs are removed from the developmental pipeline for their clinical use due to low solubility and permeability. Conventional dosage forms are found relatively unsuitable for achieving desired pharmacokinetic and pharmacodynamics profiles. Cilnidipine is 1,4 dihydropyridine derivative calcium channel blocker used for the treatment of hypertension. METHOD: The aim and objective of this study was to develop a precise and significant method in LC-MS/MS for quantification of pharmacokinetic parameters of a cilnidipine-loaded self-micro-emulsifying drug delivery system in rat plasma and simultaneously assessed pharmacodynamic characters in comparison with the marketed cilnidipine tablet. Another potential aim of this study is to reduce the dose of the drug in order to counter the dose-dependent toxicities related to chronic use. In the present study, the parent and product ion of cilnidipine was m/z 491.3\237.1. RESULT: The plasma was extracted by protein precipitation technique. The calibration standard concentrations were 1.875, 3.75, 7.50, 15.00, 30.00, 60.00ng/mL and LLOQ, low-quality control, middle-quality control and high-quality control were 1.87, 5.62, 22.50, 45.00ng/mL, respectively. The mobile phase composition was 0.1% formic acid in Milli Q water with 10mM Ammonium acetate as an aqueous solvent and 0.1% formic acid in methanol as an organic solvent. Following oral administration of optimized formulation Cmax (peak plasma concentration) was achieved 21.02±3.17ng/mL at 0.866±0.11h (Tmax), whereas in the case of marketed tablet Cmax (peak plasma concentration) was achieved 10.16±0.89ng/mL at 0.93±0.11h (Tmax). DISCUSSION: The in-vivo characterizations of the optimized SMEDDS showed significantly better pharmacokinetic parameters in Wistar rats and showed almost 2.4 times enhanced relative bioavailability as compared to the marketed tablet of cilnidipine which was observed to be correlating to our findings with noninvasive blood pressure parameter of Wistar rats.

Vitamin B12 alleviates malathion-induced toxicity in zebra fish by regulating cytochrome P450 and PgP expressions.

The indiscriminate and rampant use of pesticides has raised serious concerns regarding their toxic impact on non-target organisms which underlines need for the development of an effective antidote. Metabolic activation of organophosphate pesticides by the phase I enzyme, cytochrome P450 plays a key role in influencing pesticide-toxicity. In this study, we have investigated the effect of environmentally relevant malathion concentration (100 µg/L) alone and in combination with vitamin B12 on the expression of genes related to xenobiotic metabolism such as CYP enzymes, PgP and the key oxidative stress responsive transcription factor, Nrf2 in zebra fish liver and brain. Expressions of Nrf2-trasncribed antioxidant genes and their activities were also measured. Administration of vitamin B12 successfully revived motor functions by modulation of AchE activity. Mechanistically, vitamin B12 was demonstrated to alleviate oxidative stress which was accompanied by decreased phase-I enzyme cyp3c1 and increased pgp expressions.

COVID vaccine hesitancy among the tribal population and its determinants: A community-based study at berhampore block of Murshidabad District, West Bengal.

Background: On January 16, 2021, India rolled out the COVID vaccination drive. A successful and effective vaccination campaign requires much more than the availability of a safe and effective vaccine. This includes identifying vulnerable populations with lower vaccine confidence and identifying the drivers of vaccine hesitancy. Objective: This study aims to find out vaccine hesitancy among the tribal population regarding COVID-19 vaccination. Methods: It was an observational descriptive cross-sectional study, conducted at Manindranagar and Hatinagar gram panchayat of Berhampore Block of Murshidabad district, West Bengal, from June 2021-November 2021, among tribal people aged >18 years. A total of 198 tribal people were selected by applying the probability proportional to size sampling method. Participants were interviewed using predesigned, pretested, and semi-structured schedules. Potential predictors of hesitancy were investigated using the multivariate logistic regression model. Results: Vaccine hesitancy was present among 36.9% of the study participants. Fear of side effects (78.1%) was the most common reason of vaccine hesitancy. Only 30.8% of them received at least one dose of vaccine. Vaccine hesitancy was associated with decreased family income in the last 1 year (adjusted odds ratio [AOR] = 8.23), knowledge regarding vaccine (AOR = 0.41), adherence to COVID-appropriate behavior (AOR = 0.45), and trust on the local health-care worker (AOR = 0.32). Conclusion: Vaccine hesitancy among the tribal population is driven by a lack of knowledge and awareness. Their economic status, attitudes toward the health system, and accessibility factors may also play a major role in vaccine hesitancy. Extensive information, education, and communication activity, more involvement of health-care workers in the awareness campaign, and establishment of vaccination centers in tribal villages may be helpful.

Factors influencing contribution of geriatric persons in the society: A glance from a rural area of West Bengal.

Background: To facilitate healthy aging in India, it is important not only to acknowledge older people's contribution but also to understand their perception regarding their impact in the society along with society's attitude toward them. Objectives: This study aims to assess their self-perceived contribution in the society and the factors related with their contribution. Methods: It was an observational, descriptive, cross-sectional study, conducted at Amdanga block of North 24 Parganas district, West Bengal, during July 2021-June 2022. A total 0f 384 geriatrics were interviewed by the house-to-house survey with the help of a predesigned, pretested and semi-structured schedule. Potential predictors of contribution were investigated using the multivariate logistic regression model. Results: 78.9% of participants had contribution in the society. 85.9% were taking care of family members when they were sick. 93.2% were sharing their opinion with the family members. 86.5% were participating in various social works. 79.1% were suffering from at least one physical health problem. With increase in the number of health problems, chances of good contribution decreases. In case of self-perceived contribution in the society family type, employment, physical health and social participation are influencing the most. Conclusion: Elderly people are taking care of not only family members, but even relatives and neighbors also. They are sharing their knowledge and experience with family members and in the society. They are also contributing financially. Employment and proper health-care infrastructure for geriatric may be helpful to maximize their contribution.

Eucalyptol targets PI3K/Akt/mTOR pathway to inhibit skin cancer metastasis.

Eucalyptol (EU) is a monoterpenoid found as an active compound of many plants such as bay leaves, cardamom and is also found as a major constituent in eucalyptus oil. Although the anticancer activity of eucalyptol (EU) has been reported in a few cancer cell lines, its effect on tumor metastasis has not been studied so far. Here, we have shown that the EU has anti-metastatic activity against skin cancer cells in vitro and in vivo. EU decreases migration and invasion of skin cancer cells. Further, it reduces the expression of mesenchymal markers vimentin, snail, slug, twist, and induces the expression of epithelial marker, E-cadherin which indicates that it reverses the epithelial to mesenchymal transition. Gelatin zymography shows that the EU reduces the activity of MMP2 and MMP9. Furthermore signaling study by molecular docking and western blotting shows that EU modulates PI3K/Akt/mTOR signaling pathway. The reduction in the expression of PI3K/Akt/mTOR was enhanced by the use of the PI3K inhibitor, LY294002. In vivo, the anti-metastatic potential of EU was confirmed in C57BL/6 mouse. In conclusion, the EU inhibits migration and invasion of skin cancer by modulating PI3K/Akt/mTOR pathway both in in vitro and in vivo and might provide a new therapeutic approach in skin cancer.

Synthetic and computational efforts towards the development of peptidomimetics and small-molecule SARS-CoV 3CLpro inhibitors.

Severe Acute Respiratory Syndrome (SARS) is a severe febrile respiratory disease caused by the beta genus of human coronavirus, known as SARS-CoV. Last year, 2019-n-CoV (COVID-19) was a global threat for everyone caused by the outbreak of SARS-CoV-2. 3CLpro, chymotrypsin-like protease, is a major cysteine protease that substantially contributes throughout the viral life cycle of SARS-CoV and SARS-CoV-2. It is a prospective target for the development of SARS-CoV inhibitors by applying a repurposing strategy. This review focuses on a detailed overview of the chemical synthesis and computational chemistry perspectives of peptidomimetic inhibitors (PIs) and small-molecule inhibitors (SMIs) targeting viral proteinase discovered from 2004 to 2020. The PIs and SMIs are one of the primary therapeutic inventions for SARS-CoV. The journey of different analogues towards the evolution of SARS-CoV 3CLpro inhibitors and complete synthetic preparation of nineteen derivatives of PIs and ten derivatives of SMIs and their computational chemistry perspectives were reviewed. From each class of derivatives, we have identified and highlighted the most compelling PIs and SMIs for SARS-CoV 3CLpro. The protein-ligand interaction of 29 inhibitors were also studied that involved with the 3CLpro inhibition, and the frequent amino acid residues of the protease were also analyzed that are responsible for the interactions with the inhibitors. This work will provide an initiative to encourage further research for the development of effective and drug-like 3CLpro inhibitors against coronaviruses in the near future.

Giant Tunable Mechanical Nonlinearity in Graphene-Silicon Nitride Hybrid Resonator.

High quality factor mechanical resonators have shown great promise in the development of classical and quantum technologies. Simultaneously, progress has been made in developing controlled mechanical nonlinearity. Here, we combine these two directions of progress in a single platform consisting of coupled silicon nitride (SiNx) and graphene mechanical resonators. We show that nonlinear response can be induced on a large area SiNx resonator mode and can be efficiently controlled by coupling it to a gate-tunable, freely suspended graphene mode. The induced nonlinear response of the hybrid modes, as measured on the SiNx resonator surface is giant, with one of the highest measured Duffing constants. We observe a novel phononic frequency comb which we use as an alternate validation of the measured values, along with numerical simulations which are in overall agreement with the measurements.

Validation of a questionnaire on problematic use of smartphones among a rural population of West Bengal.

BACKGROUND: While a smartphone can be a hugely productive tool, excessive use of this device can interfere with work, education, our physical and mental health, and productivity. Nowadays, we do not just use our smartphones, but we rely on them. OBJECTIVES: The present study aims to develop and validate an instrument measuring the problematic use of smartphones among adults in a rural area of West Bengal, India. METHODS: The questionnaire on problematic use of smartphone is a self-designed tool. The items were selected by literature review. The psychometric properties of the questionnaire were assessed by content validity, construct validity, and reliability. Exploratory factor analysis was performed to identify the factors. RESULTS: Forty-two items were generated by literature review. After final analysis, the main questionnaire contained 28 items with 5 domains, namely "impulsive use of phone," "dependence," "impaired control," "denial," "decreased productivity," and "emotional attachment." The Cronbach's alpha value for three domains was found to be >0.7 and >0.8 for the other three domains. CONCLUSION: Excessive mobile phone use is associated with various adverse consequences which is emerging as a public health problem in a large number of population in India. Problematic use of smartphone questionnaire is a valid and reliable tool to assess the pattern of mobile use among Indian population.

TGFß mediated LINC00273 upregulation sponges mir200a-3p and promotes invasion and metastasis by activating ZEB1.

Transforming growth factor ß (TGFß) is a prominent cytokine that promotes tumor progression by activating epithelial-to-mesenchymal transition (EMT). This study indicated that TGFß exerted metastasis by inducing zinc finger E-box binding homeobox 1 (ZEB1) and a long noncoding RNA, LINC00273, expressions in A549 cells. Knocking down LINC00273 diminished TGFß induced ZEB1 expression as well as metastasis. Mechanistically, LINC00273 acted as a molecular sponge of microRNA (miR)-200a-3p which liberate ZEB1 to perform its prometastatic functions. LINC00273 knockdown and miR200a3p mimic transfection of A549 cells were used for validating the link between TGFß and LINC00273 induced metastasis. RNA pulldown and luciferase assay were performed to establish mir200a-3p-LINC00273 interaction. High expressions of LINC00273, TGFß, and ZEB1 with concurrent low miR200a-3p expression had been verified in vivo and in patient samples. Overall, LINC00273 promoted TGFß-induced lung cancer EMT through miR-200a-3p/ZEB1 feedback loop and may serve as a potential target for therapeutic intervention in lung cancer metastasis.

A Nuclear-Localized Naphthalimide-Based Fluorescent Light-Up Probe for Selective Detection of Carbon Monoxide in Living Cells.

A nuclear-localized fluorescent light-up probe, NucFP-NO2, was designed and synthesized that can detect CO selectively in an aqueous buffer (pH 7.4, 37 °C) through the CO-mediated transformation of the nitro group into an amino-functionalized moiety. This probe triggered a more than 55-fold "turn-on" fluorescence response to CO without using any metal ions, e.g., Pd, Rh, Fe, etc. The enhanced response is highly selective over a variety of relevant reactive oxygen, nitrogen, and sulfur species and also various biologically important cationic, anionic, and neutral species. The detection limit of this probe for CO is as low as 0.18 µM with a linear range of 0-70 µM. Also, this fluorogenic probe is an efficient candidate for monitoring intracellular CO in living cells (RAW 264.7, A549 cells), and the fluorescence signals predominantly localize in the nuclear region.

A Lysosome-Targetable Fluorescence Sensor for Ultrasensitive Detection of Hg2+ in Living Cells and Real Samples.

A new lysosome-targetable fluorescence sensor, Lyso-HGP, was designed and synthesized based on 4-methyl-2,6-diformylphenol as a fluorophore. Lyso-HGP displays highly sensitive fluorescent detection of Hg2+ in HEPES buffer solution (10 mM, DMSO 1%) of pH 7.0 at 37 °C due to the formation of highly fluorescent formyl-functionalized derivative Lyso-HGP-CHO. The sensor triggered a "turn-on" fluorescence response to Hg2+ with a simultaneous increase of fluorescence intensity by 180-fold just after 10 min. The response is very selective over a variety of biologically relevant cations, anions, molecules, and competitive toxic heavy metal cations. The limit of detection (LOD) was calculated as low as 6.82 nM. So, it can be utilized to detect this toxic heavy metal in biology and environmental samples in an aqueous buffer medium. Also, the sensor is able to monitor the subcellular distribution of Hg2+ specifically localized in the lysosome's compartment in the MCF7 human breast cancer cell line by fluorescence microscopy.

Low density culture of mammalian primary neurons in compartmentalized microfluidic devices.

This paper demonstrates the fabrication of a compartmentalized microfluidic device with docking sites to position a single neuron or a cluster of 5-6 neurons along with varying length of microgrooves and the optimization process for culturing primary mammalian neurons at low densities. The principle of centrifugation was employed to situate cells in desired locations followed by the application of a fluid flow to remove the extra or unwanted cells lying in the vicinity of the located neurons. The neuronal cell density was optimized by seeding 103 cells and 104 cells/microfluidic device. The speed of centrifugation was optimized as 1500 rpm for 1 min and a cell density of greater than or equal to 104 cells/microfluidic device was found to be suitable for loading maximum number of docking sites. The outcomes of the simulated experiments was found to be in compliance with the experimemtal verifications. Furthermore, the cells cultured within the microfluidic device were assessed for immunocytochemical staining and the axonal growth was quantified with the help of an Axofluidic software. Although, several in vitro microfluidic platforms have been developed that facilitate the investigations where communication between neurons or between neurons and other cell types is concerned, none of the partitioned devices so far has reported the presence of docking sites along with an array of grooves of varying lengths. These physically connected but fluidically isolated compartmentalized microfluidic devices may serve us in analysing the activity of a low density of neurons and the influence of axonal length in setting up a communication with other cell type.This platform is useful to gain insights into the processes of synapse formation, axonal guidance, cell-cell interaction, to name a few.

Interplay of Coriolis effect with rheology results in unique blood dynamics on a compact disc.

We investigate the influence of rotational forces on blood dynamics in a microfluidic device. The special confluence of Coriolis force and blood rheology is brought forth by analyzing the flow at different hematocrit (volume fraction of red blood cells) levels and rotational speeds. We further study the effects of channel layout and alignment with regard to the axis of rotation to understand this intricate interplay. We provide a sound basis for efficient designing of a lab on a compact disc (lab on CD) platform by harnessing the effects of Coriolis force at relatively much lower rotational speeds, in sharp contrast with the reported findings where Coriolis effects have been considered to be effective only for exceptionally high rotational speeds. Our results show that over certain intermediate regimes of rotational speeds, the flow profiles for different hematocrit levels are noticeably different. This, in turn, could be harnessed as a possible diagnostic signature of the hematocrit (or equivalently, packed cell volume) level, without necessitating the deployment of chemical consumables, in an energy efficient paradigm.

Application of laser-induced breakdown spectroscopy (LIBS) coupled with PCA for rapid classification of soil samples in geothermal areas.

The Manuguru geothermal area, located in the Telangana state, is one of the least explored geothermal fields in India. In this study, characterization of the soil samples is carried out by laser-induced breakdown spectroscopy (LIBS) coupled with analytical spectral-dependent principal component analysis. A total of 20 soil samples were collected both from near the thermal discharges as well as away from the thermal manifestations. LIBS spectra were recorded for all the collected soil samples and principal component analysis (PCA) was applied to easily identify the emission lines majorly responsible for variety classification of the soil samples. In this submission, a modified PCA was developed which is based on the spectral truncation method to reduce the huge number of spectral data obtained from LIBS. The PCA bi-plot on the LIBS data reveals the presence of two different clusters. One cluster represents the soil samples collected from the close vicinity of the thermal manifestations whereas the other cluster contains the soil samples collected away from the thermal sprouts. PCA performed on the chemical dataset of the soil samples also reveals the same clustering of the soil samples. Both LIBS and chemical analysis data shows that soil samples near the thermal waters are found to be enriched in B, Sr, Cs, Rb, Fe, Co, Al, Si, Ti, Ru, Mn, Mg, Cu, and Eu concentrations compared to the soil samples located away from thermal manifestations. This study demonstrates the potential use of LIBS coupled with PCA as a tool for variety discrimination of soil samples in a geothermal area. LIBS is shown to be a viable real-time elemental characterization technology for these samples, avoiding the rigorous dissolution required by other analytical techniques.

Cellular growth and tube formation of HTR8/SVneo trophoblast: effects of exogenously added fatty acid-binding protein-4 and its inhibitor.

Adequate placental angiogenesis is critical for the establishment of the placental circulation and thus for normal feto-placental growth and development. Fatty acid-binding protein-4 (FABP4) plays a pro-angiogenic role in endothelial cells; however, very little information is available in placental first trimester trophoblast cells. Here we report that exogenously added FABP4 (exo-FABP4) stimulated tube formation (as a measure of in vitro angiogenesis) in HTR8/SVneo trophoblastic cells. HTR-8/SVneo cells were incubated in the presence of exogenously added FABP4 at different concentrations and time points. Cellular growth, proliferation, in vitro tube formation, expression of growth stimulatory-, fatty acid transporters, and angiogenic genes were investigated. Internalization of exo-FABP4 was carried out using immunocytochemistry. Radioactive fatty acid uptake was determined in the presence and absence of FABP4 metabolic inhibitor. Exo-FABP4 (10-100 ng/ml) stimulated proliferation of HTR8/SVneo cells as compared to control. Exo-FABP4 dose dependently increased growth and viability of the cells to the similar extent as done by 50 µM of arachidonic acid. Exo-FABP4-induced tube formation and proliferation were significantly inhibited by FABP4 (BMS309403) inhibitor. Exo-FABP4 stimulated the expression of growth stimulatory genes such as tissue inhibitor of matrix metalloproteinases-1 (TIMP1), insulin-like growth factor 1 (IGF1), and also prokineticin 2 (PROK2), the pro-angiogenic mediators in these cells. In addition, expressions of genes associated with proliferation and differentiation such as sonic hedgehog (SHH) and WNT1 inducible signalling pathway protein 1 (WISP1) were significantly expressed when cells were exposed to exo-FABP4. Our findings reveal a pro-angiogenic role of FABP4 in first trimester placental trophoblast cells and its regulation may have impact in placental physiology.

Parkia javanica Extract Induces Apoptosis in S-180 Cells via the Intrinsic Pathway of Apoptosis.

Parkia javanica is a leguminous tree, various parts of which are used as food and folklore medicine by the ethnic groups of northeastern India. The present study investigates the in vitro and in vivo anticancer effect of aqueous methanol extract of P. javanica fruit (PJE). HPLC analysis was done to establish the fingerprint chromatogram of PJE and its in vitro radical scavenging activity was measured. PJE caused significant cytotoxicity in sarcoma-180 (S-180), A549, AGS, and MDA-MB435S cancer cells in vitro. Exploration of the mechanistic details in S-180 cells suggested that the reduced cell viability was mediated by induction of apoptosis. Increased expression of proapoptotic proteins such as p53, p21, Bax/Bcl2, cytochrome c (Cyt c), caspase 9, and cleaved poly(ADP-ribose) polymerase, and decrease in proliferative and antiapoptotic markers (Ki-67, Proliferating Cell Nuclear Antigen [PCNA], Bcl-2) validated the anticancer effect of PJE. A decline in the relative fluorescence emission upon staining S-180 cells with Rhodamine 123 (Rh 123), enhanced expression of cytosolic Cyt c and mitochondrial Bax, and inhibition of apoptosis in the presence of caspase-9 inhibitor in PJE-treated cells indicated intrinsic pathway of apoptosis. Liver function test and hepatic antioxidant enzymes demonstrated non-toxicity of PJE. Finally, the detection of PJE in sera by HPLC confirmed its bioavailability.

Tube formation in the first trimester placental trophoblast cells: Differential effects of angiogenic growth factors and fatty acids.

The study aims to investigate whether cytosolic fatty acid-binding protein-4 (FABP4) is involved in angiogenic growth factors- and fatty acid-induced tube formation in first trimester placental trophoblast cells, HTR8/SVneo. We determined the tube formation both at basal as well as stimulated levels in the absence and presence of inhibitors of FABP4 and VEGF signaling pathways. Basal level of tube formation was maximally reduced in the presence of 50 µM of FABP4 inhibitor compared with those by VEGF signaling pathway inhibitors (rapamycin, L-NAME, and p38 MAP kinase inhibitor). Whereas docosahexaenoic acid, 22:6n-3 (DHA)-, and VEGF-induced tube formation was maximally inhibited by p38 MAP kinase inhibitor (63.7 and 34.5%, respectively), however, leptin-induced tube formation was inhibited maximally by FABP4 inhibitor (50.7%). ANGPTL4 and oleic acid (OA)-induced tube formation was not blocked by any of these inhibitors. The FABP4 inhibitor inhibited cell growth stimulated by DHA, leptin, VEGF, and OA (P < 0.05) but was not affected by ANGPTL4. VEGF, leptin, and OA also increased FABP4 protein level in these cells, though the uptake of fatty acids by these cells was not affected by the presence of FABP4 inhibitor. Our data demonstrate that FABP4 may be involved in part in the basal level, and stimulated tube formation by VEGF, DHA, and leptin, whereas it has little or no effect in ANGPTL4- and OA-induced tube formation in these cells. Thus, FABP4 may play a differential role in fatty acids and angiogenic growth factors-mediated tube formation in the first trimester trophoblast cells in vitro.

Prospective Evaluation of Fractional Carbon Dioxide Laser Treatment of Mature Burn Scars, Post-traumatic Scars, and Post-acne Scars.

BACKGROUND: Annually, around 100 million patients worldwide acquire scars, some of which can cause significant problems. Various treatment interventions, such as topical scar creams, steroids, laser therapy, and surgery, have been developed to manage these scars. This study was conducted to evaluate the effectiveness of fractional CO2 laser treatment by assessing outcomes using the Patient Observer Scar Assessment Scale (POSAS) and clinical photographs. MATERIALS AND METHODS: A total of 47 patients were included in the study, divided into three groups: a post-acne scar group with 14 patients, a post-burn scar group with 17 patients, and a post-traumatic scar group with 16 patients. Detailed histories were taken, and clinical examinations were performed and recorded on a prepared proforma. Aesthetic outcomes were evaluated based on clinical photographs, and total patient and observer scores were recorded using POSAS at baseline, and after one and three months. POSAS comprises two components: the observer scale (POSAS-O) and the patient scale (POSAS-P). Fractional CO2 laser treatments were performed in each group, with sessions repeated every four weeks for three consecutive sessions. Data were analyzed using the paired t-test for before-and-after comparisons in each study group. Welch's ANOVA test was used for comparisons among the three groups at a significance level of p=0.05, using MS Excel (Microsoft Corporation, Redmond, Washington) and IBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, New York). RESULTS: The mean age for men was 26.38 ± 8.19 years and for women 22.21 ± 6.38 years. The study comprised 34 female patients (72.34%) and 13 male patients (27.66%). The mean POSAS observer and patient scales were recorded and compared for all three types of scars from baseline to three months. The mean percentage change in POSAS-O and POSAS-P (total score) in relation to different scar sites was recorded. The most significant difference in mean percentage change, statistically significant (p-value < 0.05), was observed for facial scars, followed by scars on the neck, and was minimal for scars on the hand, in both observer and patient groups. Even a single session of fractional CO2 laser therapy had profound effects on the overall quality of scars. CONCLUSION: Fractional carbon dioxide laser therapy improves the quality of scars and produces significant improvements in skin texture, with better effects on post-traumatic scars than on post-burn and post-acne scars. Future studies are needed to better understand the mechanism of action and to optimize the doses and timing of therapy.