Melatonin Mitigates Cisplatin-Induced Submandibular Gland Damage by Inhibiting Oxidative Stress, Inflammation, Apoptosis, and Fibrosis.

BACKGROUND: The study aims to examine the possible effect of melatonin against cisplatin-induced submandibular degeneration in experimental rats exploring its ameliorative mechanisms. METHODS: Rats were classified into four experimental groups; control group; melatonin group; cisplatin group; and cisplatin+melatonin group. Submandibular tissues were collected. Biochemical, histopathological, and immunohistopathological examination and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis were performed. RESULTS: The results indicate that intraperitoneal administration of melatonin (30 mg/kg body weight) alongside cisplatin significantly elevated submandibular glands (SMG) and reduced glutathione (GSH) and superoxide dismutase (SOD) levels (p < 0.001), while it reduced malondialdehyde (MDA) levels, NF-κB gene expression, the protein level of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), immunoexpression of low-dose cyclooxygenase-2 (Cox-2), and CD68. Moreover, melatonin reduced immune and gene expression of alpha-smooth muscle actin (α-SMA), immunoexpression of caspase-3, and gene expression of Bax in comparison to the cisplatin group. CONCLUSION: Melatonin attenuated cisplatin-induced submandibular destruction alleviating SMG oxidative stress, inflammation, and fibrosis in addition to halting cellular apoptosis, sheds light on its usage in clinical application.

Evaluating Patient Satisfaction and Quality of Life After Undergoing Laparoscopic Cholecystectomy in Al-Qunfudhah Governorate, Saudi Arabia.

BACKGROUND: Gallstone disease, commonly referred to as cholelithiasis, is a prevalent medical condition that has substantial global implications. Due to its numerous benefits, such as cheaper costs and shorter hospital stays, laparoscopic cholecystectomy (LC) has replaced open surgery as the most often performed surgical method for treating a range of biliary problems in wealthy countries. Any medical procedure's long-term patient well-being must be assessed, starting with the quality of life (QoL), patient satisfaction, and postoperative healing. AIM: The current study aims to evaluate patient satisfaction and QoL after undergoing LC in Al-Qunfudhah Governorate. METHODS:  A cross-sectional study was conducted targeting all patients who underwent LC in Al-Qunfudhah Governorate during the period from January to March 2024. The online survey was initiated by the study researchers after an intensive literature review and experts' consultation. The validated questionnaire was uploaded online using Google Forms and distributed electronically via social media apps. RESULTS: The current study included records of 200 participants where the highest proportion falls within the 26 to 35 age group, comprising 57 individuals (28.5%). In terms of gender, males represent the majority, with 109 participants (54.5%). A total of 122 individuals (61.0%) reported being satisfied with their procedures. Conversely, 18 patients (9.0%) expressed dissatisfaction. The majority of participants under investigation expressed satisfaction with their overall QoL after undergoing LC, with 84 patients (42.0%) reporting satisfaction and 67 patients (33.5%) reporting being very satisfied. Additionally, only a small proportion of participants expressed dissatisfaction or very dissatisfaction Conclusion: In summary, the current study demonstrated high satisfaction with the LC treatment and highly reported QoL, which were mostly attributable to a number of factors such as the staff's cooperation, the lack of severe problems, and the sufficiency of the pre-surgery information supplied.

Assessment of Knowledge and Awareness Levels of Lipoma and Simple Surgical Excision Among Adults in Makkah Region, Saudi Arabia.

Background Lipoma is a soft tissue tumor primarily composed of fat cells. These slow-growing, painless, subcutaneous nodules can occur in any place in the body where fat is present. Our study aims to assess the awareness, knowledge, and attitudes of Makkah region inhabitants regarding lipomas and the surgical excision method. Methodology This study used a cross-sectional methodology to evaluate the general public's knowledge regarding lipomas and the surgical excision method using a self-administered questionnaire in the Makkah region from January to April 2024. Results A total of 367 participants were included, with the majority (56.10%) aged between 18 and 29 years. The survey revealed that 48.50% had heard about lipomas, 42.80% lacked any knowledge about them, and 26.70% acquired their information via social media. Furthermore, 31.60% believed it to affect both genders equally, 46.60% admitted uncertainty, 20.40% correctly identified that lipomas can occur at any age, and 39.80% were uncertain. Overall, 57.20% correctly identified lipomas as benign tumors composed of fat cells. Opinions diverged on whether lipomas cause pain, with 46.90% being uncertain. Moreover, 25.90% of respondents thought that surgery was the sole option for removing a lipoma, while 38.10% recognized the risk of lipoma recurrence after surgical removal. Overall, 85.60% reported never being diagnosed with a lipoma, while 4.10% had been diagnosed, predominantly with single lipomas 6.00%. There were significant differences in the participants' marital status, with widowed people exhibiting the greatest awareness level, followed by single people. Conclusions Our study findings indicate a moderate level of awareness about lipomas among residents of the Makkah region. However, there are significant gaps in understanding various aspects of lipomas, including their characteristics, treatment options, and demographic distribution.

Awareness of Bariatric Sleeve Gastrectomy Complications Among the General Population of Saudi Arabian Regions.

Sleeve gastrectomy (SG) is a type of procedure called bariatric surgery that provides large weight loss and has a positive impact on diseases associated with obesity. However, it has brought several complications that have an impact on those undergoing surgery, which are classified into intraoperative and postoperative issues. The study's goal is to assess the Saudi Arabian population's awareness of SG consequences. This study assessed the general population's knowledge in Saudi Arabia in 2023 using a cross-sectional approach. The total number of participants was 1,013, the majority of whom were individuals between the ages of 18 and 25 (471, 46%), and females (692, 68%). A total of 692 (68%) participants showed awareness of BMI; in addition, 987 (97%) were aware of gastric sleeve surgery, and 538 (53%) understood its indications correctly. Regarding SG complications, approximately 821 (81%) of participants showed awareness. There were significant associations between knowledge of gastric sleeve surgery and residence in the northern region of Saudi Arabia. In conclusion, our study indicated that the general population is aware of the complications of gastric sleeve surgery, but it found a deficiency in their knowledge about BMI.

Thyroid Cancer Knowledge and Awareness in Saudi Arabia: A Cross-Sectional Study.

Background Thyroid cancer incidence has been increasing worldwide over the last few decades. It is the most common endocrine cancer and is most common among females. The study contributes to filling the knowledge gap among Saudi people regarding thyroid cancer. Objectives This research aims to investigate the level of thyroid cancer knowledge and awareness in Saudi Arabia, identify potential knowledge gaps, and develop targeted strategies for enhancing public awareness and education. Methods A cross-sectional, voluntary online survey was conducted from 1st August 2023 to 1st October 2023 among residents living in Saudi Arabia over 18 years of age. The participants included were 2030 respondents. Data analysis was performed using RStudio (R version 4.3.0; R Foundation for Statistical Computing, Vienna, Austria). Results Among the participants, the majority were female (60.4%). A total of 49.7% of the individuals reported having a moderate to high level of knowledge about thyroid cancer. While 63.9% knew the association of a lump in the neck to thyroid cancer, 82.6% affirmed to consult a doctor upon discovering a lump, 72.1% knew that regular monitoring of neck lumps is crucial for early diagnosis and treatment of precancerous conditions, 38.7% were aware of females being prone to thyroid cancer, and 59.2% were aware of the link between lifestyle and increased risk. Higher awareness scores were positively associated with female gender, previously having thyroid function tests done, and previously undergoing a US scan of the thyroid. Conclusion In this study, Saudi individuals are reported to lack some aspects of knowledge and perception of thyroid cancer. This study emphasizes filling the existing knowledge gap in thyroid cancer awareness in the Saudi population.

Novel Insights about Synergistic Effect of Zamzam Water with SGL2 Inhibitors on Wound Healing in STZ-Induced Diabetic Rats: The Role of anti-Inflammatory and Proangiogenic Effects.

Background: Hyperglycemia usually impairs wound healing by dysregulating the inflammatory response and angiogenesis. This study aimed to examine the synergistic effect of dapagliflozin and Zamzam water (ZW) on the healing of diabetic wounds and to explore their anti-inflammatory and proangiogenic effects.Materials and methods: A full-thickness excisional wound was made on the backs of all groups after two weeks of diabetes induction. Forty rats were divided into five groups, with eight rats per group; Group 1: Control non-diabetic rats; Group II: Untreated diabetic rats; Group III: Diabetic rats drinking ZW; Group IV: Diabetic rats receiving an oral dose of 1 mg/kg dapagliflozin; and Group V: Received both dapagliflozin and ZW. The healing of diabetic wounds was assessed by measuring wound closure, oxidative stress markers, immunohistochemical staining of NF-ßB, VEGF, CD34, CD45, Ki-67, and eNOS, gene expression of MMP-9, TGF-ß1, EGF-b1, FGF, and Col1A1, protein levels of TNFα, IL-1ß, IL6, Ang II, and HIF-1α by ELISA assay, and histological examination with H & E and Masson's trichrome. Combined treatment with dapagliflozin and ZW significantly (p < 0.05) enhanced the wound closure and antioxidant enzyme level, with apparent histological improvement, and shortened the inflammatory stage of the diabetic wound by decreasing the level of inflammatory markers NF-κB, TNF-α, IL-1ß, IL6, and CD45. Therefore, it improved angiogenesis markers VEGF, CD34, eNOS, EGF-ß1, FGF, Ang II, and HIF-1α, increasing Ki-67 cellular proliferation. Moreover, it enhanced the remodeling stage by increasing MMP-2, TGF-ß1, and Col1A1 levels compared to diabetic rats.

Phytochemical analysis of Origanum majorana L. extract and investigation of its antioxidant, anti-inflammatory and immunomodulatory effects against experimentally induced colitis downregulating Th17 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Origanum majorana L. is a member of the Lamiaceae family and is commonly used in Egyptian cuisine as a seasoning and flavor enhancer. It is also recognized as a well-known traditional medicine in Egypt and is widely used for treating abdominal colic due to its antispasmodic properties. However, the protective effects of Origanum majorana L. against ulcerative colitis and its underlying mechanisms remain unclear. AIM OF THE STUDY: This study aimed to identify the biologically active components present in methanol extracts of Origanum majorana L. using gas chromatography/mass spectrometry (GC/MS). Additionally, it aimed to investigate the therapeutic effects of these extracts on acetic acid-induced ulcerative colitis and elucidate the potential mechanisms involved. MATERIALS AND METHODS: We conducted a GC-MS analysis of the methanolic extract obtained from Origanum majorana L. Thirty-two male rats were included in the study and divided into four experimental groups, with eight rats in each group: sham, UC, UC + O. majorana, and UC sulfasalazine. After euthanizing the rats, colon tissue samples were collected for gross and microscopic examinations, assessment of oxidative stress, and molecular evaluation. GC-MS analysis identified 15 components in the extracts. Pretreatment with O. majorana L. extract and sulfasalazine significantly improved the disease activity index (DAI) and resulted in notable improvements in macroscopic and microscopic colon findings. Additionally, both treatments demonstrated preventive effects against colonic oxidative damage by reducing the levels of malondialdehyde (MDA) and increasing the levels of the antioxidant systems superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), which operate through the Nrf2/HO-1 signaling pathway. Moreover, these treatments downregulated the colonic inflammatory cascade by inhibiting NFκB, TNFα, IL-1ß, IL6, IL23, IL17, COX-2, and iNOS, subsequently leading to downregulation of the JAK2/STAT3 signaling pathway and a decrease in the Th17 cell response. Furthermore, a reduction in the number of apoptotic epithelial cells that expressed caspase-3 was observed. CONCLUSION: pretreatment with O. majorana L. extract significantly ameliorated acetic acid-induced ulcerative colitis. This effect could be attributed to the protective, antioxidant, anti-inflammatory, and anti-apoptotic properties of the extract.

Adult Knowledge About Postoperative Complications of Rhinoplasty in the Western Region of Saudi Arabia.

Background Rhinoplasty, a prevalent cosmetic surgical procedure worldwide, is not exempt from associated risks and complications, as with any other surgery. In light of the surging demand for rhinoplasty amongst young adults, it is imperative to acknowledge that the procedure can engender various complications that can be classified as either early or late complications. Examples of early complications include epistaxis and periorbital ecchymosis, while late complications may manifest as enophthalmos or septal perforation. The present study endeavors to gauge the knowledge of rhinoplasty complications among adult residents of the Western region of Saudi Arabia. Methods To achieve the research objectives, a cross-sectional study design was implemented, utilizing a self-administered online questionnaire. The study targeted male and female adults aged 18 years and above residing in the Western region of Saudi Arabia. The questionnaire comprised of 14 items, categorized into socio-demographic and rhinoplasty postoperative complications sections, respectively. Results The study gathered responses from a total of 968 participants, of which 60.95% fell within the age range of 18-30 years. The majority of participants identified as female (77.89%), and Saudi citizens constituted the vast majority of the respondents (96.28%). Among the participants, 22.62% expressed a desire to undergo rhinoplasty, whereas 77.38% indicated no interest in the procedure. Of those who sought rhinoplasty, the majority favored having the surgery performed by a skilled physician (81.74%). Notably, participants exhibited a relatively high level of awareness regarding the postoperative complications of rhinoplasty, with respiratory issues being the most widely recognized complication (66.63%). Conversely, headache, nausea, and vomiting were the least familiar complications (100%). Conclusion The study findings reveal a considerable knowledge gap among adults residing in the Western region of Saudi Arabia concerning rhinoplasty's possible postoperative complications. The results underscore the pressing need to establish comprehensive educational and awareness-raising programs to equip individuals contemplating the procedure with the requisite information to make informed decisions. Future research endeavors could delve into the underlying determinants that drive the desire for rhinoplasty and assess potential interventions geared toward augmenting individuals' comprehension and knowledge of the procedure.

Diacerein mitigates renal ischemia/reperfusion injury via inhibition of renal inflammation, dendritic cells maturation and apoptosis: the role of TLR4/NF-kB/NLRP3/IL-1beta signaling pathway / La diacereína mitiga la lesión por isquemia/reperfusión renal a través de la inhibición de la inflamación renal, la maduración de las células dendríticas y la apoptosis: el papel de la vía de señalización TLR4/NF-kB/NLRP3/IL-1beta

SUMMARY: One of the reasons for acute kidney damage is renal ischemia. Nevertheless, there are limited protective and therapeutic approaches for this problem. Diacerein is an anti-inflammatory drug characterized by numerous biological activities. We aimed to determine the ameliorative impact of diacerein on renal ischemia/reperfusion injury (I/R) condition, exploring the underlying mechanisms. Twenty-four male rats were allotted into four groups (n= 6): sham group; Diacerein (DIA) group; I/R group, in which a non-crushing clamp occluded the left renal pedicle for 45 min, and the right kidney was nephrectomized for 5 min before the reperfusion process; I/R + diacerein group, injected intraperitoneally with 50 mg diacerein/kg i.m 30 minutes prior to I/R operation. Ischemia/ reperfusion was found to affect renal function and induce histopathological alterations. The flow cytometry analysis demonstrated an elevated expression of innate and mature dendritic cells in I/R renal tissues. Moreover, upregulation in the expression of the inflammatory genes (TLR4, Myd88, and NLRP3), and overexpression of the pro-inflammatory cytokines (IL-1β), apoptotic (caspase-3) and pyroptotic (caspase-1) markers were observed in I/R-experienced animals. The aforementioned deteriorations were mitigated by pre-I/R diacerein treatment. Diacerein alleviated I/R-induced inflammation and apoptosis. Thus, it could be a promising protective agent against I/R.

La isquemia renal es una de los motivos del daño renal agudo. Sin embargo, los enfoques protectores y terapéuticos para este problema son limitados. La diacereína es un fármaco antiinflamatorio caracterizado por numerosas actividades biológicas. Nuestro objetivo fue determinar el impacto de mejora de la diacereína en la condición de lesión por isquemia/ reperfusión renal (I/R), explorando los mecanismos subyacentes. Veinticuatro ratas macho se distribuyeron en cuatro grupos (n= 6): grupo simulado; grupo de diacereína (DIA); grupo I/R, en el que una pinza no aplastante ocluyó el pedículo renal izquierdo durante 45 min, y el riñón derecho fue nefrectomizado durante 5 min antes del proceso de reperfusión; Grupo I/R + diacereína, inyectado por vía intraperitoneal con 50 mg de diacereína/kg i.m. 30 min antes de la operación I/R. Se encontró que la isquemia/ reperfusión afecta la función renal e induce alteraciones histopatológicas. El análisis de citometría de flujo demostró una expresión elevada de células dendríticas innatas y maduras en tejidos renales I/R. Además, se observó una regulación positiva en la expresión de los genes inflamatorios (TLR4, Myd88 y NLRP3) y una sobreexpresión de las citoquinas proinflamatorias (IL-1β), marcadores apoptóticos (caspasa-3) y piroptóticos (caspasa-1) en animales con experiencia en I/R. Los deterioros antes mencionados fueron mitigados por el tratamiento previo a la diacereína I/R. La diacereína alivió la inflamación y la apoptosis inducidas por I/R. Por lo tanto, podría ser un agente protector prometedor contra I/R.

Activation of SIRT-1 Pathway by Nanoceria Sheds Light on Its Ameliorative Effect on Doxorubicin-Induced Cognitive Impairment (Chemobrain): Restraining Its Neuroinflammation, Synaptic Dysplasticity and Apoptosis.

Chemo fog is one of the most serious health concerns encountered by cancer survivors receiving doxorubicin (DOX)-based chemotherapy. Oxidative stress, neuroinflammation, apoptosis and impairment of synaptic plasticity are regarded as the key factors implicated in DOX-induced cognitive impairment. This research aimed to assess the possible neuroprotective effect of cerium oxide nanoparticles (CeNPs) against DOX-induced neurotoxicity. Forty-eight rats were divided into four groups (12 rats/group): control group, CeNPs group (received oral CeNPs solution (35 mg/kg) daily for 4 weeks), and DOX group (were administered DOX intraperitoneally (2 mg/kg, once/week for 4 weeks)) and DOX+ CeNPs group. The findings revealed that CeNPs mitigated behavioral alterations in DOX-induced cognitive deficit. Additionally, CeNPs alleviated the histopathological abnormalities in hippocampus and ameliorated DOX-induced neuroinflammation by downregulating the expression of NF-κB, TNF-α, IL-1ß and IL6. In addition, CeNPs antagonized the apoptosis through reducing the protein expression of cytochrome c and caspase 3. In addition, it stimulated the antioxidant defense, as indicated by upregulating the expression of the Nrf2, HO-1 and PGC-1α genes. CeNPs improved synaptic plasticity via acting on the BDNF. These actions were related through the modification of SIRT-1 expression. Based on the aforementioned results, CeNPs antagonized the doxorubicin-induced neurodegeneration by its antioxidant, anti-inflammatory and antiapoptotic effects, alongside its SIRT-1 mediated mechanisms.

Blocking Wnt as a therapeutic target in mice model of skin cancer.

Wnt pathway plays an important role in controlling metabolism in cancer cells. It acts as positive modulator for both cell inflammation, through activation of NFκB, and fibrosis, through activation of TGF-ß. Therefore, the aim of this study is to investigate the therapeutic effects of blocking Wnt pathway by IWP12 on skin cancer by studying its effects on skin cancer-induced inflammation and fibrosis in a mice model of skin cancer. Skin cancer was induced by application of 7,12-dimethylbenz[a]anthracene (DMBA) and croton oil on the dorsal skin of mice. Dorsal skin was removed for estimation of gene and protein expression of Wnt, ß-catenin, SMAD, TGF-ß, NFκB, TNF-α, IL-4 and IL-10. Part of the skin is stained with hematoxylin/eosin for assessment of cell structure. Treatment of mice with IWP12 completely blocked Wnt in skin cancer mice without affecting the control mice. Skin of tumorigenic mice showed marked skin hyperkeratosis, parakeratosis, acanthosis and dysplasia. Treatment with IWP12 markedly attenuated epidermal atypia and hyperplasia. In addition, IWP12 reduced expression of ß-catenin, SMAD, TGF-ß, NFκB and TNF-α associated with increase in the expression of IL-4 and IL-10. In conclusion, blocking Wnt production ameliorated skin cancer via blocking pro-inflammatory cytokines and enhancing the anti-inflammatory cytokines. Moreover, blocking Wnt attenuated skin cancer-induced activation of fibrosis pathway.

Antitumor activity of sulforaphane in mice model of skin cancer via blocking sulfatase-2.

Although there are many treatment options for skin cancer, the chemotherapeutic agents for skin cancer are linked with many adverse effects as well as the development of multidrug resistance. Sulforaphane is an isothiocyanate, which is found in cruciferous vegetables. Consumption of sulforaphane-rich diet has been linked to inhibition of UV-exposed skin carcinogenesis. Therefore, the goal of this study was to determine the ability of sulforaphane to reduce skin cancer in mice through inhibition of sulfatase-2 enzyme. Epicutaneous application of 7,12-dimethylbenz (a) anthracene was performed on the shaved dorsal skin of mice followed by croton oil. Sulforaphane (9 µmol/mouse/day) was administered to mice orally. Skin was removed from the dorsal area for assessment of sulfatase-2, glypican-3, heparan sulphate proteoglycans (HSPGs), nuclear factor (NF)κB, nuclear factor E2-related factor 2 (Nrf2), tumor necrosis factor (TNF)-α, IL-1ß and caspase-3. In addition, skin sections were stained with haematoxylin/eosin, Mallory and cytokeratin immunostaining. We found that, sulforaphane blocked sulfatase-2 activity, leading to significant elevation in HSPGs as well as significant reduction in glypican-3. In addition, sulforaphane significantly activated Nrf2 and reduced both the gene and protein expression of NFκB, TNF-α, IL-1ß and caspase-3. In parallel, stained sections obtained from skin cancer mice treated with sulforaphane showed significant reduction in hyperkeratosis, acanthosis and epithelial dysplasia. The collective results indicate that sulforaphane suppresses skin cancer via blocking sulfatase-2 with subsequent elevation in HSPGs and reduction in glypican-3. Moreover, sulforaphane attenuated skin cancer-induced activation of inflammatory and apoptotic pathways.