Guillain-Barré syndrome after COVID-19 vaccination: A systematic review and analysis of case reports.

INTRODUCTION: Cases of Guillain-Barré Syndrome (GBS) have been believed to be associated with the novel COVID-19 infection, and also with the following vaccines developed against the infection. Our work aims to investigate the incidence of GBS after COVID-19 vaccination, and describe its clinical characteristics and potential confounders. METHODS: An electronic search was conducted through four databases: PubMed, Scopus, medRxiv, and Google Scholar for all case reports and case series describing after COVID-19 vaccine administration. All published articles from inception until November 1st, 2022 were included. Differences between groups were assessed using Pearson chi-square test. Modified Erasmus GBS Outcome Score (mEGOS) for the ability to walk after GBS was calculated for all cases with sufficient clinical data, and Kaplan-Meier survival analysis was performed to study the effect of vaccine type on the relationship between vaccination time and complication of GBS. RESULTS: About 103 studies describing 175 cases of GBS following COVID-19 vaccination were included. The Acute Inflammatory Demyelinating Polyradiculoneuropathy subtype was the most reported subtype with 74 cases (42.29%). The affected age group averaged around 53.59 ±18.83 years, with AMSAN occurring in a rather older group (63.88 ±20.87 years, p=0.049). The AstraZeneca vaccine was associated with AIDP (n=38, 21.71%) more than other vaccines, p=0.02. The bilateral facial palsy subtype was mostly linked to adenoviral vector vaccinations, accounting for an average of 72% of the total BFP cases. Dysesthesias was the most reported sensory complication (60%, p=0.349). Most GBS patients survived (96%, p=0.036), however, most patients had low mEGOS scores (4 ±3.57, p<0.01). On average, patients developed GBS at 13.43 ±11.45 days from vaccination (p=0.73), and survival analysis for complication of GBS into mechanical ventilation or walking impairment yielded a severely increased probability of complication after 25 days (p<0.01). Intravenous immunoglobulins (p=0.03) along with rehabilitation (p=0.19) were the most commonly used treatment. CONCLUSION: This work investigates the incidence of Guillain-Barré Syndrome after COVID-19 vaccination. Most cases occurred after receiving the AstraZeneca or Pfizer vaccines, and despite low mortality rates, ambulation was compromised in most patients. A higher risk of GBS complication is associated with an onset later than 12-13 days, particularly with Pfizer, AstraZeneca, and Moderna vaccines. No specific predisposing or prognostic factor was identified, and the relation between the COVID-19 vaccines and GBS remain unclear.

Bayesian Optimization of Booster Disinfection Scheduling in Water Distribution Networks.

Chlorine remains the most widely used disinfectant in drinking water treatment and distribution systems worldwide. To maintain a minimum residual throughout the distribution network, chlorine dosage needs to be regulated by optimizing the locations of chlorine boosters and their scheduling (i.e., chlorine injection rates). Such optimization can be computationally expensive since it requires numerous evaluations of water quality (WQ) simulation models. In recent years, Bayesian optimization (BO) has garnered considerable attention due to its efficiency in optimizing black-box functions in a wide range of applications. This study presents the first attempt to implement BO for the optimization of WQ in water distribution networks. The developed python-based framework couples BO with EPANET-MSX to optimize the scheduling of chlorine sources, while ensuring the delivery of water that satisfies water quality standards. Using Gaussian process regression to build the BO surrogate model, a comprehensive analysis was conducted to evaluate the performance of different BO methods. To that end, systematic testing of different acquisition functions, including the probability of improvement, expected improvement, upper confidence bound, and entropy search, in conjunction with different covariance kernels, including Matérn, squared-exponential, gamma-exponential, and rational quadratic, was conducted. Additionally, a thorough sensitivity analysis was performed to understand the influence of different BO parameters, including the number of initial points, covariance kernel length scale, and the level of exploration vs exploitation. The results revealed substantial variability in the performance of different BO methods and showed that the choice of the acquisition function has a more profound influence on the performance of BO than the covariance kernel.

First confirmed case of multisystem inflammatory syndrome in adult in Egypt.

Key Clinical Message: Our case report demonstrates extremely uncommon data associated with MIS-A, such as cholestatic jaundice, anemia, and quickly progressing pneumonia. IVIG and pulse steroid medications are the best treatments for improving clinical outcomes. Abstract: We report a case of multiple organ dysfunctions due to MIS-A in an adult with a history of suspected COVID-19. Our case demonstrates extremely uncommon data associated with MIS-A, such as cholestatic jaundice, anemia, and quickly progressing pneumonia. IVIG and pulse steroid medications are the best treatments for improving clinical outcomes.

A rare association: Obesity hypoventilation syndrome with myasthenia gravis and systemic lupus erythematosus, case report.

Background: Shrinking lung syndrome (SLS) is an uncommon complication of systemic lupus erythematosus (SLE) that has also been seen in other autoimmune diseases and is linked with a high risk of acute or chronic respiratory failure. Alveolar hypoventilation in the presence of obesity-hypoventilation syndrome, systemic lupus erythematosus (SLE), and myasthenia gravis (MG) is uncommon and poses a diagnostic and therapeutic challenge. Case report: We reported a 33-year-old female patient from Saudi Arabia who suffered from obesity, bronchial asthma, newly diagnosed essential hypertension, type 2 diabetes mellitus, with recurrent acute alveolar hypoventilation, secondary to obesity hypoventilation syndrome and mixed autoimmune disease (systemic lupus erythematosus and myasthenia gravis), based on the correct constellation of clinical findings and laboratory evidence. Conclusion: The interesting aspect of this case report: is the presentation of the overlap of obesity hypoventilation syndrome and shrinking lung syndrome due to systemic lupus erythematosus with generalized and respiratory muscle dysfunction due to myasthenia gravis with good outcomes after therapy.

RIS-Enabled Secret Key Generation for Secured Vehicular Communication in the Presence of Denial-of-Service Attacks.

Wireless communication has become an integral part of modern vehicles. However, securing the information exchanged between interconnected terminals poses a significant challenge. Effective security solutions should be computationally inexpensive, ultra-reliable, and capable of operating in any wireless propagation environment. Physical layer secret key generation has emerged as a promising technique, which leverages the inherent randomness of wireless-channel responses in amplitude and phase to generate high-entropy symmetric shared keys. The sensitivity of the channel-phase responses to the distance between network terminals makes this technique a viable solution for secure vehicular communication, given the dynamic behavior of these terminals. However, the practical implementation of this technique in vehicular communication is hindered by fluctuations in the communication link between line-of-sight (LoS) and non-line-of-sight (NLoS) conditions. This study introduces a key-generation approach that uses a reconfigurable intelligent surface (RIS) to secure message exchange in vehicular communication. The RIS improves the performance of key extraction in scenarios with low signal-to-noise ratios (SNRs) and NLoS conditions. Additionally, it enhances the network's security against denial-of-service (DoS) attacks. In this context, we propose an efficient RIS configuration optimization technique that reinforces the signals received from legitimate users and weakens the signals from potential adversaries. The effectiveness of the proposed scheme is evaluated through practical implementation using a 1-bit RIS with 64×64 elements and software-defined radios operating within the 5G frequency band. The results demonstrate improved key-extraction performance and increased resistance to DoS attacks. The hardware implementation of the proposed approach further validated its effectiveness in enhancing key-extraction performance in terms of the key generation and mismatch rates, while reducing the effect of the DoS attacks on the network.

Acute kidney injury in Coronavirus disease-19 related pneumonia in the intensive care unit: a retrospective multicenter study, Saudi Arabia.

Background: Acute kidney injury (AKI) poses a significant morbidity and mortality risk to critically ill COVID-19 patients. The aim of this study was to investigate the incidence, predictors, and outcomes of AKI in patients admitted to the intensive care unit (ICU) with critically ill COVID-19 pneumonia. Methods: A multicenter retrospective study in Saudi Arabia of adult patients aged at least 18 years diagnosed with COVID-19 pneumonia and admitted to the intensive care unit between May 2020 and May 2021 was conducted. The occurrence of AKI and associated risk factors, the need for continous renal replacement therapy (CRRT), and the outcome were reported. Results: The study included 340 patients admitted to the ICU with COVID-19. Their mean age was 66.7±13.4 years, ranging from 49 to 84 years, and most of them were men (63.8%). The most common concomitant diseases were hypertension (71.5%), diabetes (62.4%), IHD (37.6%), CKD (20%), heart failure (19.4%), and 81.2% suffered from ARDS. AKI occurred in 60.3% of patients, 38% were stage 1, 16.6% were stage 2, and 45.4% were stage 3. Approximately, 39% of patients required CRRT, out of which 76.2% were stage 3, which was significantly higher than the other stages (p<0.001). AKI patients suffered significantly from asthma and had lower levels of C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), and blood urea nitrogen (BUN) and higher creatinine levels than patients without AKI (p<0.05 all). The overall mortality rate was 39.4%, and the mortality rate was significantly higher in patients with AKI than in patients without AKI (48.3% versus 25.9%; p<0.001). Conclusion: AKI is common in adults admitted to the ICU with COVID-19 and is associated with an increased risk of death. Early detection of AKI and appropriate treatment can positively impact COVID-19 outcome. CRRT is the preferred dialysis method in critically ill ICU patients with AKI.

Increased Expression of the Δ133p53ß Isoform Enhances Brain Metastasis.

The Δ133p53ß isoform is increased in many primary tumors and has many tumor-promoting properties that contribute to increased proliferation, migration and inflammation. Here we investigated whether Δ133p53ß contributed to some of the most aggressive tumors that had metastasized to the brain. Δ133p53ß mRNA expression was measured in lung, breast, melanoma, colorectal metastases and, where available, the matched primary tumor. The presence of Δ133p53ß expression was associated with the time for the primary tumor to metastasize and overall survival once the tumor was detected in the brain. Δ133p53ß was present in over 50% of lung, breast, melanoma and colorectal metastases to the brain. It was also increased in the brain metastases compared with the matched primary tumor. Brain metastases with Δ133p53ß expressed were associated with a reduced time for the primary tumor to metastasize to the brain compared with tumors with no Δ133p53ß expression. In-vitro-based analyses in Δ133p53ß-expressing cells showed increased cancer-promoting proteins on the cell surface and increased downstream p-AKT and p-MAPK signaling. Δ133p53ß-expressing cells also invaded more readily across a mock blood-brain barrier. Together these data suggested that Δ133p53ß contributes to brain metastases by making cells more likely to invade the brain.

Contactless WiFi Sensing and Monitoring for Future Healthcare - Emerging Trends, Challenges, and Opportunities.

WiFi sensing has received recent and significant interest from academia, industry, healthcare professionals, and other caregivers (including family members) as a potential mechanism to monitor our aging population at a distance without deploying devices on users' bodies. In particular, these methods have the potential to detect critical events such as falls, sleep disturbances, wandering behavior, respiratory disorders, and abnormal cardiac activity experienced by vulnerable people. The interest in such WiFi-based sensing systems arises from practical advantages including its ease of operation indoors as well as ready compliance from monitored individuals. Unlike other sensing methods, such as wearables, camera-based imaging, and acoustic-based solutions, WiFi technology is easy to implement and unobtrusive. This paper reviews the current state-of-the-art research on collecting and analyzing channel state information extracted using ubiquitous WiFi signals, describing a range of healthcare applications and identifying a series of open research challenges, including untapped areas of research and related trends. This work aims to provide an overarching view in understanding the technology and discusses its use-cases from a perspective that considers hardware, advanced signal processing, and data acquisition.

Stereotactic Radio Surgery, Embolization and Conservative Management for Cerebral Arteriovenous Malformation: A New Zealand Experience of Long-Term Outcomes.

OBJECTIVE: Cerebral arteriovenous malformations (AVMs) can be treated by microsurgery, stereotactic radiosurgery (SRS) as a stand-alone procedure, or combining embolization and conservative management. This single-center, retrospective review explored the outcomes of patients treated with SRS alone, embolization before SRS (ESRS), or conservative management for cerebral AVMs. METHODS: Demographic details, Spetzler-Martin grade, SRS dose, obliteration, time to obliteration, imaging modality, rebleed, disease-specific mortality, and post-SRS complications were collected. Chi-square tests of independence and 1-way analysis of variance/Kruskal-Wallis tests were performed. RESULTS: Two-hundred and thirty-nine patients were treated with SRS alone, 37 were treated with ESRS, and 83 were conservatively managed. Obliteration rates were 78% (SRS alone) and 70% (ESRS). Rebleed rates were comparable among SRS alone (4%), ESRS (0%), and conservative management (8%). Disease-specific mortality rates were significantly lower for SRS alone (1%) and ESRS (0%) compared with conservative management (6%, X2 [2, n = 358] = 7.50, P = 0.024). Post-SRS complications occurred with SRS alone only and included radiation necrosis (n = 5), cavernous malformations (n = 2), and stroke (n = 1). Obliteration, rebleed, and disease-specific mortality rates were comparable among pediatric (<18 years), nonelderly (18-59 years), and elderly (≥60 years) age groups. CONCLUSIONS: Findings suggest that SRS and ESRS are safe and effective treatments for cerebral AVM (when quantified by obliteration, rebleed, and disease-specific mortality rates). With multinational, prospective, randomized controlled trials with long follow-up periods, the effectiveness and safety of SRS and ESRS compared with conservative management for AVM will be further clarified.

Right Unilateral Versus Bilateral Electroconvulsive Therapy in Patients With Clinical Depression.

Introduction Electroconvulsive therapy (ECT) is a functional treatment for a significant mental illness that involves a momentary application of electrical stimulation to induce generalized seizures. The use of right unilateral (RUL) and bilateral (BL) ECT has been controversial. Thus, the study aimed at comparing the effectiveness of RUL ECT and BL ECT in treating depression. Methodology A longitudinal study was conducted between September 2016 and January 2021 at a tertiary care hospital in Sindh, Pakistan. All patients over the age of 18 with clinically diagnosed depression in the last month were included in the study. Baseline depression scores and post-treatment scores were determined using Hamilton Depression Rating Scale (HDRS). All patients were assigned to each treatment group. Group A was administered right unilateral electroconvulsive therapy, while group B was administered bilateral electroconvulsive therapy. Adverse effects were documented right after treatment, at four hours, and then one day after therapy. Depression severity was determined after each ECT session using the HDRS scale. Electroconvulsive therapy was discontinued when an HDRS score of 10 was achieved.  Results  The mean HDRS score at baseline in the bilateral ECT group was 24.99 ± 3.938, which lowered to 17.56 ± 2.65 by the 3rd session, 12.45 ± 3.76 by the 6th session, and to 11.86 ± 2.3 by the end of treatment (p<0.0001). Similarly, the right unilateral ECT was equally effective in improving the depressive symptoms (p<0.0001). There was no significant difference between the efficacy of bilateral and unilateral placements of electrodes in electroconvulsive therapy (p=0.116).

5G-enabled contactless multi-user presence and activity detection for independent assisted living.

Wireless sensing is the state-of-the-art technique for next generation health activity monitoring. Smart homes and healthcare centres have a demand for multi-subject health activity monitoring to cater for future requirements. 5G-sensing coupled with deep learning models has enabled smart health monitoring systems, which have the potential to classify multiple activities based on variations in channel state information (CSI) of wireless signals. Proposed is the first 5G-enabled system operating at 3.75 GHz for multi-subject, in-home health activity monitoring, to the best of the authors' knowledge. Classified are activities of daily life performed by up to 4 subjects, in 16 categories. The proposed system combines subject count and activities performed in different classes together, resulting in simultaneous identification of occupancy count and activities performed. The CSI amplitudes obtained from 51 subcarriers of the wireless signal are processed and combined to capture variations due to simultaneous multi-subject movements. A deep learning convolutional neural network is engineered and trained on the CSI data to differentiate multi-subject activities. The proposed system provides a high average accuracy of 91.25% for single subject movements and an overall high multi-class accuracy of 83% for 4 subjects and 16 classification categories. The proposed system can potentially fulfill the needs of future in-home health activity monitoring and is a viable alternative for monitoring public health and well being.

Chronic elevation of cardiac troponin I predicts the extent of coronary disease in hemodialysis patients presenting with acute enzyme elevation.

Introduction: Elevation of cardiac troponin I (cTn-I) is associated with coronary artery disease (CAD) in asymptomatic patients with end-stage renal disease (ESRD) receiving hemodialysis. We aim to investigate the diagnostic value of chronically elevated cTn-I in ESRD patients presenting with an acute rise in serum cTn-I levels. Methods: We performed a retrospective analysis of 364 patients. Using coronary angiography, we correlated baseline elevation of cTn-I with the severity of CAD when hemodialysis patients present with acute symptomatic elevation in serum cTn-I. Results: In hemodialysis patients presenting with a rise in serum cTn-I above baseline levels, 59% had severe CAD, and 17% had no angiographic evidence of CAD. Hemodialysis patients with severe CAD had significantly higher baseline cTn-I levels compared to patients with non-severe CAD or normal coronaries (p < 0.0001). Baseline elevation of cTn-I in the severe CAD group was correlated with the degree of CAD occlusion (r2 0.56, p < 0.0001), fitting a positive linear model. Furthermore, baseline cTn-I differentiates between patients with and without severe CAD with a test accuracy of 0.72 (95% CI, 0.69-0.75, p < 0.001). At a value of ≥0.2 ng/mL (cutoff for myocardial necrosis), the specificity of baseline cTn-I for underlying severe CAD was 0.95. Conclusions: Elevated baseline cTn-I has good accuracy for anticipating more advanced angiographic CAD when hemodialysis patients present with a symptomatic rise in serum cTn-I above baseline levels. Baseline elevation of cTn-I can be used for cardiac disease risk management in hemodialysis patients presenting with symptoms suggestive of CAD.

Intronic TP53 Polymorphisms Are Associated with Increased Δ133TP53 Transcript, Immune Infiltration and Cancer Risk.

We investigated the influence of selected TP53 SNPs in exon 4 and intron 4 on cancer risk, clinicopathological features and expression of TP53 isoforms. The intron 4 SNPs were significantly over-represented in cohorts of mixed cancers compared to three ethnically matched controls, suggesting they confer increased cancer risk. Further analysis showed that heterozygosity at rs1042522(GC) and either of the two intronic SNPs rs9895829(TC) and rs2909430(AG) confer a 2.34-5.35-fold greater risk of developing cancer. These SNP combinations were found to be associated with shorter patient survival for glioblastoma and prostate cancer. Additionally, these SNPs were associated with tumor-promoting inflammation as evidenced by high levels of infiltrating immune cells and expression of the Δ133TP53 and TP53ß transcripts. We propose that these SNP combinations allow increased expression of the Δ133p53 isoforms to promote the recruitment of immune cells that create an immunosuppressive environment leading to cancer progression.

The oncogene BCL6 is up-regulated in glioblastoma in response to DNA damage, and drives survival after therapy.

The prognosis for people with the high-grade brain tumor glioblastoma is very poor, due largely to low cell death in response to genotoxic therapy. The transcription factor BCL6, a protein that normally suppresses the DNA damage response during immune cell maturation, and a known driver of B-cell lymphoma, was shown to mediate the survival of glioblastoma cells. Expression was observed in glioblastoma tumor specimens and cell lines. When BCL6 expression or activity was reduced in these lines, increased apoptosis and a profound loss of proliferation was observed, consistent with gene expression signatures suggestive of anti-apoptotic and pro-survival signaling role for BCL6 in glioblastoma. Further, treatment with the standard therapies for glioblastoma-ionizing radiation and temozolomide-both induced BCL6 expression in vitro, and an in vivo orthotopic animal model of glioblastoma. Importantly, inhibition of BCL6 in combination with genotoxic therapies enhanced the therapeutic effect. Together these data demonstrate that BCL6 is an active transcription factor in glioblastoma, that it drives survival of cells, and that it increased with DNA damage, which increased the survival rate of therapy-treated cells. This makes BCL6 an excellent therapeutic target in glioblastoma-by increasing sensitivity to standard DNA damaging therapy, BCL6 inhibitors have real potential to improve the outcome for people with this disease.

Enhanced recovery of low concentration protein and peptide solutions on ultra-low binding microplates.

SiO2 Medical Products (SIO) developed PureWARE™ Ultra-Low Binding (ULB) plasma-treated microplates with the combined benefits of enhanced protein recovery and reduced extractables. This study demonstrates enhanced protein recoveries, but at ten-times lower protein concentration, or 0.1 nM, compared with a prior study. In addition, no significant effect on enhanced protein recovery of plasma-treated microplates was observed in a long-term stability study carried out for 26 months under ambient storage conditions. Furthermore, recovery of three different peptide solutions, in the concentration range of 1.5-12 nM, was also shown to be enhanced on plasma-treated microplates relative to standard polypropylene microplates.

Diaphragm-sparing effect of the infraclavicular subomohyoid block vs low volume interscalene block. A randomized blinded study.

BACKGROUND: Both low volume interscalene and infraclavicular-subomohyoid blocks were suggested to provide shoulder analgesia with low risk of phrenic nerve block. The aim of this study was to compare the frequency of the phrenic nerve block between these two techniques. METHOD: Seventy-two patients scheduled for shoulder arthroscopy were included in this randomized controlled blind study. Before induction of general anesthesia, patients received low volume interscalene block using 5 mL of ropivacaine 0.5% (LVS group) or infraclavicular-subomohyoid block using 25 mL of ropivacaine 0.5% (ISO group). The diaphragmatic excursion was measured (using ultrasound) before the block and after surgery. If the ratio of postoperative to pre-block excursions was <25%, a phrenic nerve block was concluded. Secondary outcomes were: the duration of analgesia, the 24-hour morphine requirement, and patient satisfaction. RESULTS: The phrenic nerve was blocked in 88.9% of patients in LVS group vs 5.6% in ISO group (P < 0.001). There was no significant difference between the two groups with regard to the duration of analgesia, the morphine consumption, and the patient satisfaction. CONCLUSION: Compared with the low volume interscalene block, the infraclavicular subomohyoid block resulted in a significantly less frequent phrenic nerve block and with no difference in postoperative analgesia. Therefore, it may be relevant to consider for patients who cannot tolerate a phrenic nerve block.

Elevation of the TP53 isoform Δ133p53ß in glioblastomas: an alternative to mutant p53 in promoting tumor development.

As tumor protein 53 (p53) isoforms have tumor-promoting, migration, and inflammatory properties, this study investigated whether p53 isoforms contributed to glioblastoma progression. The expression levels of full-length TP53α (TAp53α) and six TP53 isoforms were quantitated by RT-qPCR in 89 glioblastomas and correlated with TP53 mutation status, tumor-associated macrophage content, and various immune cell markers. Elevated levels of Δ133p53ß mRNA characterised glioblastomas with increased CD163-positive macrophages and wild-type TP53. In situ-based analyses found Δ133p53ß expression localised to malignant cells in areas with increased hypoxia, and in cells with the monocyte chemoattractant protein C-C motif chemokine ligand 2 (CCL2) expressed. Tumors with increased Δ133p53ß had increased numbers of cells positive for macrophage colony-stimulating factor 1 receptor (CSF1R) and programmed death ligand 1 (PDL1). In addition, cells expressing a murine 'mimic' of Δ133p53 (Δ122p53) were resistant to temozolomide treatment and oxidative stress. Our findings suggest that elevated Δ133p53ß is an alternative pathway to TP53 mutation in glioblastoma that aids tumor progression by promoting an immunosuppressive and chemoresistant environment. Adding Δ133p53ß to a TP53 signature along with TP53 mutation status will better predict treatment resistance in glioblastoma. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Liver targeted therapies for hepatocellular carcinoma prior to transplant: contemporary management strategies.

Hepatocellular carcinoma (HCC) is an aggressive neoplastic disease that has been rapidly increasing in incidence. It usually occurs in the background of liver disease, and cirrhosis. Definitive therapy requires surgical resection. However, in majority of cases surgical resection is not tolerated, especially in the presence of portal hypertension and cirrhosis. Orthotopic liver transplant (OLT) in well selected candidates has been accepted as a viable option. Due to a relative scarcity of donors compared to the number of listed recipients, long waiting times are anticipated. To prevent patients with HCC from dropping out from the transplant list due to progression of their disease, most centers utilize loco-regional therapies. These loco-regional therapies(LRT) include minimally invasive treatments like percutaneous thermal ablation, trans-arterial chemoembolization, trans-arterial radio-embolization or a combination thereof. The type of therapy or combination used is determined by the size and location of the HCC and Barcelona Clinic Liver Cancer (BCLC) classification. The data regarding the efficacy of LRT in reducing post-transplant recurrence or disease-free survival is limited. This article reviews the available therapies, their strengths, limitations, and current use in the management of patients with hepatocellular carcinoma awaiting transplant.

Protective effect of curcumin against ultraviolet A irradiation­induced photoaging in human dermal fibroblasts.

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in skin, resulting in photoaging. Natural botanicals have gained considerable attention due to their beneficial protection against the harmful effects of UV irradiation. The present study aimed to evaluate the ability of curcumin (Cur) to protect human dermal fibroblasts (HDFs) against ultraviolet A (UVA)­induced photoaging. HDFs were treated with 0­10 µM Cur for 2 h and subsequently exposed to various intensities of UVA irradiation. The cell viability and apoptotic rate of HDFs were investigated by MTT and flow cytometry assays, respectively. The effect of UVA and Cur on the formation of reactive oxygen species (ROS), malondialdehyde levels, which are an indicator of ROS, and the levels/activity of antioxidative defense proteins, including glutathione, superoxide dismutase and catalase, were evaluated using 2',7'-dichlorofluorescin diacetate and commercial assay kits. Furthermore, western blotting was performed to determine the levels of proteins associated with endoplasmic reticulum (ER) stress, the apoptotic pathway, inflammation and the collagen synthesis pathway. The results demonstrated that Cur reduced the accumulation of ROS and restored the activity of antioxidant defense enzymes, indicating that Cur minimized the damage induced by UVA irradiation in HDFs. Furthermore, western blot analysis demonstrated that Cur may attenuate UVA­induced ER stress, inflammation and apoptotic signaling by downregulating the protein expression of glucose­regulated protein 78, C/EBP­homologous protein, nuclear factor­κB and cleaved caspase­3, while upregulating the expression of Bcl­2. Additionally, it was demonstrated that Cur may regulate collagen metabolism by decreasing the protein expression of matrix metalloproteinase (MMP)­1 and MMP­3, and may promote the repair of cells damaged as a result of UVA irradiation through increasing the protein expression of transforming growth factor­ß (TGF­ß) and Smad2/3, and decreasing the expression of the TGF­ß inhibitor, Smad7. In conclusion, the results of the present study indicate the potential benefits of Cur for the protection of HDFs against UVA­induced photoaging and highlight the potential for the application of Cur in skin photoprotection.