Unveiling the multifaceted antiproliferative efficacy of Cichorium endivia root extract by dual modulation of apoptotic and inflammatory genes, inducing cell cycle arrest, and targeting COX-2.

Chicory (Cichorium endivia L. divaricatum) is a renowned medicinal plant traditionally used for various ailments, yet the pharmacological potential of its roots, particularly in terms of antitumor activity, remains elusive. In the present study, we explore, for the first time, the metabolomic profile of ethanolic extract from Cichorium endivia roots (CIR) and further unveil its antiproliferative potential. The untargeted phytochemical analysis UPLC/T-TOF-MS/MS identified 131 metabolites in the CIR extract, covering acids, amino acids, flavonoids, alkaloids, nucleotides, and carbohydrates. The antiproliferative activity of the CIR extract was tested in 14 cancer cell lines, revealing significant cytotoxicity (IC50: 2.85-29.15 µg mL-1) and a high selectivity index. Among the cells examined, the CIR extract recorded the most potent antiproliferative activity and selectivity toward HepG2 and Panc-1 cells, with an IC50 of 2.85 µg mL-1 and 3.86 µg mL-1, respectively, and SI > 10. Insights into the mode of action of the antiproliferative activity revealed that CIR extract induces cell arrest in the S phase while diminishing cell distribution in the G0/G1 and G2/M phases in HepG-2 and Panc-1 cells. Flow cytometric and RT-PCR analysis revealed that the CIR extract significantly triggers apoptosis and modulates the expression of pro-apoptotic and anti-apoptotic genes. Furthermore, the CIR extract exhibited a pronounced anti-inflammatory activity, as evidenced by down-regulating key cytokines in LPS-induced RAW 264.7 cells and selectively inhibiting the COX-2 enzyme. Finally, the CIR extract showed a robust total antioxidant capacity, together with potent free radicals and metal scavenging properties, highlighting its role in alleviating oxidative stress. Taken together, this study highlights the multifaceted therapeutic potential of CIR extract as a natural-based antitumor supplement.

Microvascular Thrombosis in Celiac Disease: Is Free Flap an Option? Case Presentation and Literature Review.

Celiac disease is an autoimmune disease that occurs due to gluten intolerance. The prevalence of breast cancer among celiac disease patients is the same as in the general population. It is of note that breast cancer is the most common type of cancer in women. Following mastectomy, these patients visit plastic surgeons for breast reconstruction. Based on various factors, autologous reconstruction using abdominal-based flaps is the best option. Patients with celiac disease have a high incidence of thromboembolic disorders, which may prevent plastic surgeons from doing breast reconstruction with free flaps. We present a case of a patient with celiac disease who underwent a free flap for breast reconstruction with an uneventful course after using our routine postoperative protocol. This case report highlights that patients with celiac disease cannot be denied the option of breast reconstruction with free flaps.

Deciphering the therapeutic potential of trimetazidine in rheumatoid arthritis via targeting mi-RNA128a, TLR4 signaling pathway, and adenosine-induced FADD-microvesicular shedding: In vivo and in silico study.

Rheumatoid arthritis (RA) is a debilitating autoimmune condition characterized by chronic synovitis, joint damage, and inflammation, leading to impaired joint functionality. Existing RA treatments, although effective to some extent, are not without side effects, prompting a search for more potent therapies. Recent research has revealed the critical role of FAS-associated death domain protein (FADD) microvesicular shedding in RA pathogenesis, expanding its scope beyond apoptosis to include inflammatory and immune pathways. This study aimed to investigate the intricate relationship between mi-RNA 128a, autoimmune and inflammatory pathways, and adenosine levels in modulating FADD expression and microvesicular shedding in a Freund's complete adjuvant (FCA) induced RA rat model and further explore the antirheumatoid potency of trimetazidine (TMZ). The FCA treated model exhibited significantly elevated levels of serum fibrogenic, inflammatory, immunological and rheumatological diagnostic markers, confirming successful RA induction. Our results revealed that the FCA-induced RA model showed a significant reduction in the expression of FADD in paw tissue and increased microvesicular FADD shedding in synovial fluid, which was attributed to the significant increase in the expression of the epigenetic miRNA 128a gene in addition to the downregulation of adenosine levels. These findings were further supported by the significant activation of the TLR4/MYD88 pathway and its downstream inflammatory IkB/NFB markers. Interestingly, TMZ administration significantly improved, with a potency similar to methotrexate (MTX), the deterioration effect of FCA treatment, as evidenced by a significant attenuation of fibrogenic, inflammatory, immunological, and rheumatological markers. Our investigations indicated that TMZ uniquely acted by targeting epigenetic miRNA128a expression and elevating adenosine levels in paw tissue, leading to increased expression of FADD of paw tissue and mitigated FADD microvesicular shedding in synovial fluid. Furthermore, the group treated with TMZ showed significant downregulation of TLR4/MYD88 and their downstream TRAF6, IRAK and NF-kB. Together, our study unveils the significant potential of TMZ as an antirheumatoid candidate, offering anti-inflammatory effects through various mechanisms, including modulation of the FADD-epigenetic regulator mi-RNA 128a, adenosine levels, and the TLR4 signaling pathway in joint tissue, but also attenuation of FADD microvesicular shedding in synovial fluid. These findings further highlight the synergistic administration of TMZ and MTX as a potential approach to reduce adverse effects of MTX while improving therapeutic efficacy.

Revolutionizing and identifying novel drug targets in Citrobacter koseri via subtractive proteomics and development of a multi-epitope vaccine using reverse vaccinology and immuno-informatics.

Citrobacter koseri is a gram-negative rod that has been linked to infections in people with significant comorbidities and immunocompromised immune systems. It is most commonly known to cause urinary tract infections. Thus, the development of an efficacious C. koseri vaccine is imperative, as the pathogen has acquired resistance to current antibiotics. Subtractive proteomics was employed during this research to identify potential antigenic proteins to design an effective vaccine against C. koseri. The pipeline identified two antigenic proteins as potential vaccine targets: DP-3-O-acyl-N-acetylglucosamine deacetylase and Arabinose 5-phosphate isomerase. B and T cell epitopes from the specific proteins were forecasted employing several immunoinformatic and bioinformatics resources. A vaccine was created using a combination of seven cytotoxic T cell lymphocytes (CTL), five helper T cell lymphocyte (HTL), and seven linear B cell lymphocyte (LBL) epitopes. An adjuvant (ß-defensin) was added to the vaccine to enhance immunological responses. The created vaccine was stable for use in humans, highly antigenic, and non-allergenic. The vaccine's molecular and interactions binding affinity with the human immunological receptor TLR3 were studied using MMGBSA, molecular dynamics (MD) simulations, and molecular docking analyses. E. coli (strain-K12) plasmid vector pET-28a (+) was used to examine the ability of the vaccine to be expressed. The vaccine shows great promise in terms of developing protective immunity against diseases, based on the results of these computer experiments. However, in vitro and animal research are required to validate our findings.Communicated by Ramaswamy H. Sarma.

Mangiferin (mango) attenuates AOM-induced colorectal cancer in rat's colon by augmentation of apoptotic proteins and antioxidant mechanisms.

Mangiferin (MF) is a natural C-glucosylxantone compound that has many substantial curative potentials against numerous illnesses including cancers. The present study's goal is to appraise the chemo preventive possessions of MF on azoxymethane (AOM)-mediated colonic aberrant crypt foci (ACF) in rats. Rats clustered into 5 groups, negative control (A), inoculated subcutaneously with normal saline twice and nourished on 0.5% CMC; groups B-E injected twice with 15 mg/kg azoxymethane followed by ingestion of 0.5% CMC (B, cancer control); intraperitoneal inoculation of 35 mg/kg 5-fluorouracil (C, reference rats) or nourished on 30 mg/kg (D) and 60 mg/kg (E) of MF. Results of gross morphology of colorectal specimens showed significantly lower total colonic ACF incidence in MF-treated rats than that of cancer controls. The colon tissue examination of cancer control rats showed increased ACF availability with bizarrely elongated nuclei, stratified cells, and higher depletion of the submucosal glands compared to MF-treated rats. Mangiferin treatment caused increased regulation of pro-apoptotic (increased Bax) proteins and reduced the ß-catenin) proteins expression. Moreover, rats fed on MF had significantly higher glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and lower malondialdehyde (MDA) concentrations in their colonic tissue homogenates. Mangiferin supplementation significantly down-shifted pro-inflammatory cytokines (transforming growth factor-α and interleukine-6) and up-shifted anti-inflammatory cytokines (interleukine-10) based on serum analysis. The chemo-protective mechanistic of MF against AOM-induced ACF, shown by lower ACF values and colon tissue penetration, could be correlated with its positive modulation of apoptotic cascade, antioxidant enzymes, and inflammatory cytokines originating from AOM oxidative stress insults.

Anise (Pimpinella anisum L.) attenuates azoxymethane-induced colorectal cancer by antioxidant, anti-inflammatory, and anti-apoptotic pathways in rats.

Herbal medicine is one of the most common fields explored for combating colon cancers, and Pimpinella anisum L. seeds (PAS) have been utilized widely as medicinal agents because of their increased essential oil (trans-anethole) contents. In this essence, our study investigates the toxic effect and chemoprotective potentials of PAS against azoxymethane (AOM)-induced colon cancer in rats. The toxicity trial for PAS conducted by clustering fifteen rats into three groups (five rats each): A, normal control had 10% Tween 20; B, ingested with 2 g/kg PAS; and C, supplemented with 4 g/kg PAS. The in vivo cancer trial was performed by using 30 rats (Sprague-Dawley) that were randomly adapted in five steel cages (six rats each): group A, normal controls received two subcutaneous injections of normal saline 0.09% and ingested orally 10% Tween 20; groups B-E, rats received two injections of 15 mg/kg of azoxymethane (AOM) subcutaneously in 2 weeks and treated orally with 10% Tween 20 (group B) or intraperitoneal injection of 5-fluorouracil (35 mg/kg) (group C), or orally given 200 mg/kg PAS (group D) and 400 mg/kg PAS (group E) for 8 weeks. After the scarification of rats, the colon tissues were dissected for gross and histopathological evaluations. The acute toxicity trial showed the absence of any toxic signs in rats even after 14 days of ingesting 4 g/kg of PAS. The chemoprotective experiment revealed significant inhibitory potentials (65.93%) of PAS (400 mg/kg) against aberrant crypto foci incidence that could be correlated with its positive modulation of the immunohistochemically proteins represented by a significant up-regulation of the Bax protein and a decrease of the Bcl-2 protein expressions in colon tissues. Furthermore, PAS-treated rats had notably lower oxidative stress in colon tissues evidenced by decreased MDA levels and increased antiradical defense enzymes (SOD, CAT, and GPx). The outcomes suggest 400 mg/kg PAS as a viable additive for the development of potential pharmaceuticals against colorectal cancer.

Pinostrobin attenuates azoxymethane-induced colorectal cytotoxicity in rats through augmentation of apoptotic Bax/Bcl-2 proteins and antioxidants.

Objectives: Pinostrobin (5-hydroxy-7-methoxyflavanone; PN) is a natural active ingredient with numerous biological activities extensively utilized in tumour chemotherapy. The present study investigates the chemo-preventive potentials of PN on azoxymethane-mediated colonic aberrant crypt foci in rats. Methods: Sprague Dawley rats clustered into five groups, normal control (A) and cancer controls were subcutaneously injected with normal saline and 15 mg/kg azoxymethane, respectively, and nourished on 10% tween 20 and fed on 10% tween 20; reference control (C), injected with 15 mg/kg azoxymethane and injected (intraperitoneal) with 35 mg/kg 5-fluorouracil (5-FU); D and E rat groups received a subcutaneous injection of 15 mg/kg azoxymethane and nourished on 30 and 60 mg/kg of PN, respectively. Results: The acute toxicity trial showed a lack of any abnormal signs or mortality in rats ingested with 250 and 500 mg/kg of PN. The gross morphology of colon tissues revealed significantly lower total colonic aberrant crypt foci incidence in PN-treated rats than that of cancer controls. Histological examination of colon tissues showed increased aberrant crypt foci availability with bizarrely elongated nuclei, stratified cells and higher depletion of the submucosal glands in cancer controls. PN treatment caused positive modulation of apoptotic (Bax and Bcl-2) proteins and inflammatory cytokines (TNF-α, IL-6 and IL-10). Moreover, rats fed on PN had significantly higher antioxidants (superoxide dismutase) and lower malondialdehyde concentrations in their colon tissue homogenates. Conclusion: The chemoprotective efficiency of PN against azoxymethane-induced aberrant crypt foci is shown by lower aberrant crypt foci values and higher aberrant crypt foci inhibition percentage, possibly through augmentation of genes responsible for apoptotic cascade and inflammations originating from azoxymethane oxidative stress insults.

Cytotoxicity and Radiosensitizing Potentials of Pilosulin-3, a Recombinant Ant Venom, in Breast Cancer Cells.

Venom peptides are promising agents in the development of unconventional anticancer therapeutic agents. This study explored the potential of Pilosulin-3, a recombinant peptide from the venom of the Australian jack jumper ant "Myrmecia pilosula", as a cytotoxic and radiosensitizing agent in MCF-7 and MDA-MB-231 breast cancer (BC) cell lines. Pilosulin-3's cytotoxicity was evaluated across a wide range of concentrations using a proliferation assay. Cell cycle progression and apoptosis were examined at the inhibitory concentration 25% (IC25) and IC50 of Pilosulin-3, both with and without a 4Gy X-ray irradiation dose. Radiosensitivity was assessed at IC25 using the clonogenic survival assay. The study revealed that Pilosulin-3 exerted a concentration-dependent cytotoxic effect, with IC25 and IC50 values of 0.01 and 0.5 µM, respectively. In silico screening indicated high selectivity of Pilosulin-3 peptide, which was predicted to be the most likely anticancer agent (PROB = 0.997) with low hemolytic activity (PROP = 0.176). Although Pilosulin-3 exhibited a significant (p < 0.05) G2/M cell cycle arrest in combination with radiation, there was no discernible effect on apoptosis induction or cell survival following irradiation. In conclusion, Pilosulin-3 proved to be cytotoxic to BC cells and induced a cytostatic effect (G2/M arrest) when combined with radiation. However, it did not enhance the efficacy of cell killing by irradiation. While it holds potential as a cytotoxic agent in breast cancer treatment, its application as a radiosensitizer does not find support in these results.

The Effects of Various Teaching Methods on Chest X-ray Interpretation Skills Among Medical Students and Interns: A Systematic Review.

Chest X-ray (CXR) is a common tool used in medical practice. Medical students and interns should acquire knowledge of CXR interpretation, as it is an essential diagnostic tool for a large spectrum of diseases. This systematic review aimed to compare the effect of different intervention techniques on the competency of medical students and interns to demonstrate the level of confidence and competence in interpreting common presentations of CXRs. The population, intervention, comparison, and outcomes (PICO) framework was used to formulate the review question. All related articles in five databases (PubMed, Web of Science, Scopus, Medline, and Embase) were retrieved and the search was completed in March 2023 with no limiters on date and time. The number of relevant studies was 469. A multi-level approach through the Rayyan platform was used for the screening and exclusion processes. Eleven articles were included in the systematic review consisting of eight randomized controlled trials, one quasi-experimental study, one cross-sectional study, and one interventional cohort. Results showed significant effects of teaching methods utilizing deductive or inductive approach, clinical history, patient care comfort survey, and SAFMEDS (Say-All-Fast-Minute-Every-Day-Shuffled). Contrarily, no significant effect was shown by flipped classroom models and mixed and blocked practice, peer-assisted learning vs. expert-assisted learning, and Chester, an artificial intelligence tool. This review identified beneficial approaches that may enhance the learning outcomes of interpreting CXRs for medical students and interns, highlighting the remarkable impact of SAFMEDS on medical students' ability to identify CXR findings as well as the availability and practicality of online and e-learning resources for students.

Fecal Calprotectin and Organic Gastrointestinal Disease: A Systematic Review.

This review aimed to assess the diagnostic utility of fecal calprotectin (FCP) for identifying organic gastrointestinal disease (OGID) in patients undergoing colonoscopy for gastrointestinal discomfort or active progression of inflammatory bowel disease (IBD). Studies published between January 2013 and December 2022 evaluating the clinical efficacy of FCP for differentiating OGID against functional gastrointestinal disease (FGID) were identified using PubMed, Cochrane, and Scopus databases. Clinical diagnostic studies involving individuals with lower gastrointestinal symptoms; using FCP as a diagnostic biomarker either in primary, secondary, or tertiary healthcare centers conducted either prospectively or retrospectively using stool samples (index test), contrasting FCP with a reference test, such as colonoscopy, or endoscopy, and assessed using enzyme-linked immunosorbent assay were reviewed. The included studies were subjected to the revised Quality Assessment of Diagnostic Accuracy Studies for assessing the methodological quality by two independent authors. An initial literature search yielded 545 articles rendering 417 records after removing the duplicate records. After reading the abstracts and titles, 89 articles were eligible for full-text screening. The qualitative synthesis resulted in 20 articles. The efficient use of FCP for differentiating IBD from irritable bowel syndrome was investigated in 15 studies.Two of the included studies assessed the diagnostic ability of FCP to distinguish OGID from FGID, two studies utilized patients with ulcerative colitis, and one study involved patients with Crohn's disease. Overall study quality was high for 65% of studies,moderate for 25% of studies, and low for 10% of studies. The review outlined the diagnostic accuracy of non-invasive FCP assessment for OGID in various clinical scenarios and in individuals of various ages. FCP is used as a tool for screening and monitoring in clinical practice for determining the need of further comprehensive investigations, thereby reducing the redundant use of invasive techniques.

Boric Acid (Boron) Attenuates AOM-Induced Colorectal Cancer in Rats by Augmentation of Apoptotic and Antioxidant Mechanisms.

Boric acid (BA) is a naturally occurring weak Lewis acid containing boron, oxygen, and hydrogen elements that can be found in water, soil, and plants. Because of its numerous biological potentials including anti-proliferation actions, the present investigates the chemopreventive possessions of BA on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Thirty laboratory rats were divided into 5 groups: negative control (A) received two subcutaneous inoculations of normal saline and nourished on 10% Tween 20; groups B-E had two injections of 15 mg/kg azoxymethane followed by ingestion of 10% Tween 20 (B, cancer control), inoculation with intraperitoneal 35 mg/kg 5-fluorouracil injection (C, reference group), or ingested with boric acid 30 mg/kg (D) and 60 mg/kg (E). The gross morphology results showed significantly increased total colonic ACF in cancer controls, while BA treatment caused a significant reduction of ACF values. Histopathological evaluation of colons from cancer controls showed bizarrely elongated nuclei, stratified cells, and higher depletion of the submucosal glands than that of BA-treated groups. Boric acid treatment up-surged the pro-apoptotic (Bax) expression and reduced anti-apoptotic (Bcl-2) protein expressions. Moreover, BA ingestion caused upregulation of antioxidant enzymes (GPx, SOD, CAT), and lowered MDA contents in colon tissue homogenates. Boric acid-treated rats had significantly lower pro-inflammatory cytokines (TNF-α and IL-6) and higher anti-inflammatory cytokines (IL-10) based on serum analysis. The colorectal cancer attenuation by BA is shown by the reduced ACF numbers, anticipated by its regulatory potentials on the apoptotic proteins, antioxidants, and inflammatory cytokines originating from AOM-induced oxidative damage.

Toxicity of Nab-Paclitaxel Compared to Paclitaxel in a Tertiary Hospital in Jeddah, Saudi Arabia: A Retrospective Cohort Study.

Background Nanoparticle albumin-bound paclitaxel has been developed to avoid the toxicities associated with Cremophor-solved paclitaxel. Although many studies confirm this hypothesis, there is recent evidence showing no difference between paclitaxel and nab-paclitaxel in their efficacy and safety profile. This study further assesses the toxicity of both paclitaxel and nab-paclitaxel in adult patients with breast and pancreatic cancer in a tertiary hospital in Jeddah, Saudi Arabia. These toxicities include neutropenia, anaemia, and effects on kidney and liver functions. Methods The study is a retrospective cohort study done at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, from January 2018 to December 2021, conducted on patients diagnosed with breast or pancreatic cancer treated with paclitaxel or nab-paclitaxel. Results There is a statistically significant difference between the two groups in developing anaemia, renal, and liver toxicity (P<0.05). On the other hand, there are no statistically significant differences in developing neutropenia between the two groups (P=0.084). Conclusions Nab-paclitaxel might not be better than paclitaxel in reducing the risk of neutropenia, anaemia, and liver toxicity, as predicted. Nevertheless, both medications require that the patient's renal functions be monitored during the treatment. Further studies conducted in multiple oncology centres with a larger sample are needed to evaluate the toxicity of paclitaxel and nab-paclitaxel in adult patients with breast and pancreatic cancer.

Risk of Polypharmacy and Its Outcome in Terms of Drug Interaction in an Elderly Population: A Retrospective Cross-Sectional Study.

The simultaneous use of multiple drugs-termed 'polypharmacy'-is often required to manage multiple physiological and biological changes and the interplay between chronic disorders that are expected to increase in association with ageing. However, by increasing the number of medications consumed, the risk of undesirable medication reactions and drug interactions also increases exponentially. Hence, knowledge of the prevalence of polypharmacy and the risk of potentially serious drug-drug interactions (DDIs) in elderly patients should be considered a key topic of interest for public health and health care professionals. Methods: Prescription and demographic data were collected from the electronic files of patients who were aged ≥ 65 years and attended Al-Noor Hospital in Makkah, Saudi Arabia, between 2015 and 2022. The Lexicomp® electronic DDI-checking platform was used to evaluate the patients' medication regimens for any potential drug interactions. Results: A total of 259 patients were included in the study. The prevalence of polypharmacy among the cohort was 97.2%: 16 (6.2%) had minor polypharmacy, 35 (13.5%) had moderate polypharmacy, and 201 (77.6%) had major polypharmacy. Of the 259 patients who were taking two or more medications simultaneously, 221 (85.3%) had at least one potential DDI (pDDI). The most frequently reported pDDI under category X that should be avoided was the interaction between clopidogrel and esomeprazole and was found in 23 patients (18%). The most frequently reported pDDI under category D that required therapeutic modification was the interaction between enoxaparin and aspirin, which was found in 28 patients (12%). Conclusions: It is often necessary for elderly patients to take several medications simultaneously to manage chronic diseases. Clinicians should distinguish between suitable, appropriate and unsuitable, inappropriate polypharmacy, and this criterion should be closely examined when establishing a therapeutic plan.

SARS-CoV-2 Detection and COVID-19 Diagnosis: A Bird's Eye View.

The battle against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) associated coronavirus disease 2019 (COVID-19) is continued worldwide by administering firsttime emergency authorized novel mRNA-based and conventional vector-antigen-based anti- COVID-19 vaccines to prevent further transmission of the virus as well as to reduce the severe respiratory complications of the infection in infected individuals. However; the emergence of numerous SARS-CoV-2 variants is of concern, and the identification of certain breakthrough and reinfection cases in vaccinated individuals as well as new cases soaring in some low-to-middle income countries (LMICs) and even in some resource-replete nations have raised concerns that only vaccine jabs would not be sufficient to control and vanquishing the pandemic. Lack of screening for asymptomatic COVID-19-infected subjects and inefficient management of diagnosed COVID-19 infections also pose some concerns and the need to fill the gaps among policies and strategies to reduce the pandemic in hospitals, healthcare services, and the general community. For this purpose, the development and deployment of rapid screening and diagnostic procedures are prerequisites in premises with high infection rates as well as to screen mass unaffected COVID-19 populations. Novel methods of variant identification and genome surveillance studies would be an asset to minimize virus transmission and infection severity. The proposition of this pragmatic review explores current paradigms for the screening of SARS-CoV-2 variants, identification, and diagnosis of COVID-19 infection, and insights into the late-stage development of new methods to better understand virus super spread variants and genome surveillance studies to predict pandemic trajectories.

[Retracted] Effects of nutrients on matrix metalloproteinases in human T­lymphotropic virus type 1 positive and negative malignant T­lymphocytes.

Subsequently to the publication of the above article, a concerned reader drew to the attention of the Editorial Office and the authors that certain pairings of the GAPDH western blotting control bands in Fig. 4 appeared to be strikingly similar to adjacent pairings of bands within the same gel slices; moreover, data bands featured in the HuT­2, C91­PL and Jurkat zymography blots in Fig. 5 also appeared to be remarkably similar, both comparing the bands within a given gel slice (as in the case of the Jurkat cell experiment in Fig. 5) or comparing between gel slices (as in the case of the Hut­2 cells compared with the C910PL cells in Fig. 5). The Editorial Office independently investigated these concerns, and reached the conclusion that the bands did appear strikingly similar; too similar for the appearance of the bands within these figures to have arisen by chance. Moreover, the application of a software analysis program revealed that certain of the data in Fig. 6 had also appeared in another paper published by several of the same authors in another journal at around the same time. As a result of this investigation, the Editor of International Journal of Oncology has decided that this paper should be retracted from the journal on account of a lack of confidence in the authenticity of the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 45: 2159­2166, 2014; DOI: 10.3892/ijo.2014.2638].

Role of Serum Amyloid A as a Biomarker for Predicting the Severity and Prognosis of COVID-19.

Objective: To detect biomarkers that can be used to predict COVID-19 severity to identify patients with high probability of disease progression and poor prognosis. Methods: Of the 102 patients with confirmed COVID-19 who were admitted to King Fahd General Hospital, Jeddah City, Saudi Arabia, from July 1, 2021 to August 5, 2021, 50 were included in this cross-sectional study to investigate the influence of serum amyloid A (SAA) on disease severity and survival outcomes of COVID-19 patients. Dynamic shifts in SAA, C-reactive protein (CRP), white blood cell (WBC), lymphocytes, neutrophils, biochemical markers, and disease progression were examined. At admission, and at three, five, and seven days after treatment, at least four data samples were collected from all patients, and they underwent clinical status assessments. Results: Critically ill patients showed higher SAA and CRP levels and WBC and neutrophil counts and significantly lower lymphocyte and eosinophil counts compared to the moderately/severely ill patients, especially with regard to disease progression. Similarly, nonsurvivors had higher SAA levels than survivors. The moderately/severely ill patients and the survivors had significantly higher dynamic changes in SAA compared to the critically ill patients and nonsurvivors, respectively, with differences clearly noticed on the fifth and seventh day of treatment. ROC curve analysis revealed that the combination of SAA and CRP was valuable in evaluating the disease progression and prognosis of COVID-19 patients at different time points; however, a combination of SAA and lymphocyte counts was more sensitive for disease severity prediction on admission. The most sensitive parameters for predicting survival on admission were the combination of SAA/WBC and SAA/neutrophil count. Conclusions: The study findings indicate that SAA can be used as a sensitive indicator to assess the degree of disease severity and survival outcomes of COVID-19 patients.

The Hybrid Facelift.

In facelift surgery, many surgeons tend to choose one superficial musculoaponeurotic system (SMAS) technique over another. SMAS plication augments tissue using folding, which is very useful in deflated faces. In heavy faces, SMAS-ectomy and, to an arguably further extent, full SMAS undermining and excision can reduce volume and avoid the excessive fullness that may follow plication. Not all patients present with uniform deflation or uniform fullness of the face. Some will present with a mixed picture, fullness in one area such as the cheek with deflation in another (eg, over the angle of the mandible). In those patients, plication alone may lead to undesired fullness, typically overaugmenting cheeks or angle of the mandible. SMAS elevation and excision may avoid overaugmentation (arguably better than simple SMAS-ectomy), but it is technically more demanding and consumes longer operative time. An alternative approach is suggested in this article. For those patients with "mixed" pictures, we suggest a hybrid of existing SMAS techniques, in which for each side of the face, the face is divided into upper (cheek) and lower (jawline and neck) areas. Deflated areas are addressed with plication. Full areas are addressed with SMAS undermining and excision. Although this kind of surgical approach might be practiced by some surgeons, it has not been described well in the literature. In a series of 495 facelifts, the author found this "hybrid facelift" technique useful in 61 cases.

Omega 3 fatty acids - Potential modulators for oxidative stress and inflammation in the management of sickle cell disease

Abstract Objective Sickle cell disease is characterized by clinical complications resulting in vaso-occlusive crisis with prominent attributes of oxidative stress, inflammation, and pain. Inflammation is an integral part of this disease which further exacerbates the pain during a crisis. Omega-3 fatty acids are known to possess anti-inflammatory and anti-aggregatory properties and assist in diminishing the slow physiological inactivation. Methods A pilot nutritional interventional study was conducted wherein forty-three children with sickle cell disease aged 5-16 years were supplemented with omega-3 fatty acids for a period of six months. Analysis of oxidative stress, as well as inflammatory parameters, was done pre and post-supplementation. Results Increased free oxygen radical transference values depicting free radical generation is enhanced in these patients along with a reduced antioxidant defense, as seen by decreased free oxygen radical defense values. Supplementation with omega-3 fatty acids for a period of six months significantly reduced the inflammatory marker homocysteine in all patients, whereas high sensitive C reactive protein was significantly reduced only in females of the age group 11-16years. Simultaneously a significant reduction in oxidative stress parameters with a concomitant increase of antioxidant defense was observed in all patients. Conclusion The authors' findings suggest the regulatory effects of omega-3 fatty acids as cellular activators in alleviating the complications due to sickle cell disease. Omega-3 fatty acids hold promise as future therapeutic candidates in patients with sickle cell disease.

Omega 3 fatty acids - Potential modulators for oxidative stress and inflammation in the management of sickle cell disease.

OBJECTIVE: Sickle cell disease is characterized by clinical complications resulting in vaso-occlusive crisis with prominent attributes of oxidative stress, inflammation, and pain. Inflammation is an integral part of this disease which further exacerbates the pain during a crisis. Omega-3 fatty acids are known to possess anti-inflammatory and anti-aggregatory properties and assist in diminishing the slow physiological inactivation. METHODS: A pilot nutritional interventional study was conducted wherein forty-three children with sickle cell disease aged 5-16 years were supplemented with omega-3 fatty acids for a period of six months. Analysis of oxidative stress, as well as inflammatory parameters, was done pre and post-supplementation. RESULTS: Increased free oxygen radical transference values depicting free radical generation is enhanced in these patients along with a reduced antioxidant defense, as seen by decreased free oxygen radical defense values. Supplementation with omega-3 fatty acids for a period of six months significantly reduced the inflammatory marker homocysteine in all patients, whereas high sensitive C reactive protein was significantly reduced only in females of the age group 11-16years. Simultaneously a significant reduction in oxidative stress parameters with a concomitant increase of antioxidant defense was observed in all patients. CONCLUSION: The authors' findings suggest the regulatory effects of omega-3 fatty acids as cellular activators in alleviating the complications due to sickle cell disease. Omega-3 fatty acids hold promise as future therapeutic candidates in patients with sickle cell disease.

Coronary artery calcium score above 250 confirms the presence of significant stenosis in coronary CT angiography of symptomatic patients.

OBJECTIVES: Evaluation of coronary artery calcium score (CACS) at multiple low and high cutoff values for the detection of significant coronary stenosis at two different cutoffs (50 and 70%) in a large number of symptomatic patients was not investigated previously in one study. This study aims to investigate if there are a correlation and statistical significance between different CACS cutoffs and the severity of coronary artery stenosis by coronary CT angiography (CCTA) in symptomatic patients. METHODS: This is a retrospective study that included all symptomatic patients who had CCTA in a tertiary care hospital over a period of 7 years. RESULTS: CCTA of 502 patients was evaluated (406 included, mean age 56.2 years); 230 were males (56.7%). The prevalence of stenosis at any percentage was 53.7%, ≥50% was 26.6% and ≥70% was 12.3%. The mean CACS was 84.5 (range 0-1860), for males was 124.5 and for females was 32.1. Patients with CACS of zero (59%) and CACS of ≥1 (41%) had a mean stenosis of 8.9% (range 0-75%) and 52.6% (range 0-100%), respectively. All patients with a CACS of ≥250 were found to have ≥50% stenosis (100% specificity and positive predictive value, 35.2% sensitivity, 81% negative predictive value and 82.6% accuracy). The percentage of stenosis increased as CACS increased with strong statistical significance (P value < 0.0001) and a positive correlation (r = 0.58). CONCLUSIONS: CACS is a valuable diagnostic tool to predict the severity of coronary artery stenosis. A cutoff value of 250 confirmed the presence of at least 50% stenosis in symptomatic patients.