Targeting tumour markers in ovarian cancer treatment.

Ovarian cancers (OC) are the most common, lethal, and stage-dependent cancers at the global level, specifically in female patients. Targeted therapies involve the administration of drugs that specifically target the alterations in tumour cells responsible for their growth, proliferation, and metastasis, with the aim of treating particular patients. Presently, within the realm of gynaecological malignancies, specifically in breast and OCs, there exist various prospective therapeutic targets encompassing tumour-intrinsic signalling pathways, angiogenesis, homologous-recombination deficit, hormone receptors, and immunologic components. Breast cancers are often detected in advanced stages, primarily due to the lack of a reliable screening method. However, various tumour markers have been extensively researched and employed to evaluate the condition, progression, and effectiveness of medication treatments for this ailment. The emergence of recent technological advancements in the domains of bioinformatics, genomics, proteomics, and metabolomics has facilitated the exploration and identification of hitherto unknown biomarkers. The primary objective of this comprehensive review is to meticulously investigate and analyze both established and emerging methodologies employed in the identification of tumour markers associated with OC.

Knowledge, Attitude, and Practice of Adult Diabetics Regarding Diabetic Foot Ulcers: A Cross-Sectional Study in Saudi Arabia.

Background Diabetic foot ulcers (DFUs) are one of the most common and fatal complications of diabetic patients with uncontrolled diabetes mellitus (DM) that may end with their feet amputation. These complications can be prevented through the adherence of diabetic patients to their diabetes management plan and by educating them about risk factors, complications of diabetic foot, and proper foot care. To develop effective health education programs to educate diabetic patients and caregivers regarding diabetic foot and its effective care, we should first identify gaps in patients' knowledge and perception of diabetic foot and evaluate their practice of foot care. Objectives This study aimed to evaluate knowledge and attitude toward DFUs and the practice of foot care among adult diabetic patients attending Al-Qunfudah Diabetes Center, Saudi Arabia, from October 2022 to March 2023. Methods A total of 403 adult diabetic patients were recruited in this cross-sectional study during their attendance at the diabetes center in Al-Qunfudah district, Saudi Arabia. The study researchers conducted a physical face-to-face interview with each diabetic patient using a validated questionnaire with closed-ended questions to collect their responses regarding their knowledge and attitude toward DFUs and their behavior toward foot care. The collected data were analyzed using IBM SPSS Statistics for Windows, version 23 (released 2015; IBM Corp., Armonk, New York, United States). Results Out of 403 diabetics, 50.4% (n = 203) had inadequate knowledge (knowledge score < 80%), 46.4% (n = 187) had negative attitudes (attitude score < 80%) toward DFUs, and the majority could not practice foot care well, with 77.7% (n = 313) giving a practice score less than 80%. Seventy patients (17.4%) self-reported a history of DFUs. Predictors of good knowledge about DFUs among diabetics include age between 30 and 59 years (odds ratio (OR) = 2.942, confidence interval (CI) 95% = 1.695-2.107, p < 0.001), marriage (OR = 3.101, CI 95% = 1.893-5.079, p < 0.001), working (OR = 5.325, CI 95% = 3.019-9.389, p < 0.001), diploma education (OR = 8.205, CI 95% = 3.332-20.203, p < 0.001), managing DM with oral drugs (OR = 2.219, CI 95% = 1.399-3.519, p < 0.001), and having no DFUs (OR = 2.712, CI 95% = 1.557-4.723, p < 0.001). Males were more likely to practice foot care well (OR = 1.925, CI 95% = 1.142-3.245, p = 0.013). Primary education (OR = 3.421, CI 95% = 1.655-7.073, p < 0.001) predicted appropriate foot care. Patients with DM for one to five years (OR = 1.995, CI 95% = 1.139-3.493, p = 0.016) and those on diet and metformin (OR = 2.133, CI 95% = 1.134-4.011, p = 0.019) were expected to have better foot care than other diabetics. Conclusion Diabetic patients in the Al-Qunfudah district of Saudi Arabia had inadequate knowledge and negative attitudes toward DFUs, and their foot care behaviors were inadequate. Furthermore, DFUs were self-reported in around 17% of diabetic patients. Specialized training programs are recommended to enhance knowledge regarding DFUs among diabetics and motivate and train them and caregivers on how to conduct proper foot care. These educational programs should target all diabetics, with an emphasis on those with DFUs, females, non-working patients, individuals who have had DM for a longer time, and illiterate diabetics. To understand the factors behind patients' negative attitudes toward diabetic foot, future qualitative research is required.

Microbial dysbiosis and the aging process: a review on the potential age-deceleration role of Lactiplantibacillus plantarum.

Gut microbiota dysbiosis has been a serious risk factor for several gastric and systemic diseases. Recently, gut microbiota's role in aging was discussed. Available preclinical evidence suggests that the probiotic bacteria Lactiplantibacillus plantarums (LP) may influence the aging process via modulation of the gut microbiota. The present review summarized compelling evidence of LP's potential effect on aging hallmarks such as oxidative stress, inflammation, DNA methylation, and mitochondrial dysfunction. LP gavage modulates gut microbiota and improves overall endurance in aging animal models. LP cell constituents exert considerable antioxidant potential which may reduce ROS levels directly. In addition, restored gut microbiota facilitate a healthy intestinal milieu and accelerate multi-channel communication via signaling factors such as SCFA and GABA. Signaling factors further activate specific transcription factor Nrf2 in order to reduce oxidative damage. Nrf2 regulates cellular defense systems involving anti-inflammatory cytokines, MMPs, and protective enzymes against MAPKs. We concluded that LP supplementation may be an effective approach to managing aging and associated health risks.

Integrated approach for detection of SARS-CoV-2 and its variant by utilizing LAMP and ARMS-PCR.

Global impact of COVID-19 pandemic has heightened the urgency for efficient virus detection and identification of variants such as the Q57H mutation. Early and efficient detection of SARS-CoV-2 among densely populated developing countries is paramount objective. Although RT-PCR assays offer accuracy, however, dependence on expansive kits and availability of allied health resources pose an immense challenge for developing countries. In the current study, RT-LAMP based detection of SARS-Cov-2 with subsequent confirmation of Q57H variant through ARMS-PCR was performed. Among the 212 collected samples, 134 yielded positive results, while 78 tested negative using RT-LAMP. Oropharyngeal swabs of suspected individuals were collected and processed for viral RNA isolation. Isolated viral RNA was processed further by using either commercially available WarmStart Master Mix or our in house developed LAMP master mix separately. Subsequently, the end results of each specimen were evaluated by colorimetry. For LAMP assays, primers targeting three genes (ORF1ab, N and S) were designed using PrimerExplorer software. Interestingly, pooling of these three genes in single reaction tube increased sensitivity (95.5%) and specificity (93.5%) of LAMP assay. SARS-CoV-2 positive specimens were screened further for Q57H mutation using ARMS-PCR. Based on amplicon size variation, later confirmed by sequencing, our data showed 18.5% samples positive for Q57H mutation. Hence, these findings strongly advocate use of RT-LAMP-based assay for SARS-CoV-2 screening within suspected general population. Furthermore, ARMS-PCR also provides an efficient mean to detect prevalent mutations against SARS-Cov-2.

Anxiolytic and antidepressant like effects of Zamzam water in STZ-induced diabetic rats, targeting oxidative stress, neuroinflammation, BDNF/ERK/CREP pathway with modulation of hypothalamo-pituitary-adrenal axis.

Introduction: Recent studies have reported a strong relationship between diabetes and anxiety- and depression-like behaviors; however, there is a lack of information on the underlying pathophysiology. Alkaline Zamzam water (ZW), which is rich in several trace elements, has neuroprotective properties. This study aimed to investigate the anxiolytic and antidepressant effects of ZW against diabetes-induced behavioral changes and shed light on the possible underlying mechanisms. Methods: Forty-eight rats were divided into four experimental groups (n = 12): group I (control group), group II (Zamzam water group), group III (diabetic group), and group IV (diabetic + Zamzam water group). Diabetes was induced by an intraperitoneal injection of 60 mg/kg streptozotocin (STZ). At the end of the experiment, the forced swimming test (FST) was used to assess depression-like effects. The elevated plus maze test (EPMT) and open field test (OFT) were performed to evaluate anxiety-like behavior. Blood levels of the hypothalamic-pituitary-adrenal (HPA) axis were measured, and prefrontal cortex and hippocampal tissue samples were removed for histological, immunohistochemical, ELISA, and Q-PCR analyses. Results: ZW significantly decreased the immobility time in the FST, indicating an antidepressant effect (p < 0.001). Additionally, ZW significantly improved the OFT and open field entry (OFE) percentages in the EPMT, increasing center crossing and decreasing grooming and fecal boli in the OFT. This indicated an anxiolytic-like effect in diabetic rats with histological improvement. Interestingly, ZW significantly increased prefrontal cortical and hippocampal levels of antioxidant enzymes and the Nrf2/HO-1 pathway. It also modulated the HPA axis by increasing cortisol and corticotropin-releasing hormone (CRH) levels, with a decrease in ACTH and an increase in monoamine neurotransmitters. Furthermore, diabetic rats that received ZW showed a decrease in the inflammatory markers TNF-α and GFAP by immunohistochemistry and in the mRNA levels of NFκB, IL-1ß, and IL6. In addition, ZW downregulated the expression of the BDNF/ERK2/CREP pathway. Conclusion: Our results suggested a neuroprotective effect of ZW against diabetes-induced anxiety- and depression-like behaviors and explored the underlying mechanisms. These findings suggest a promising therapeutic strategy for patients with diabetes who experience anxiety and depression.

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.

An Overview of Various Rifampicin Analogs against Mycobacterium tuberculosis and their Drug Interactions.

The success of the TB control program is hampered by the major issue of drug-resistant tuberculosis (DR-TB). The situation has undoubtedly been made more difficult by the widespread and multidrug-resistant (XDR) strains of TB. The modification of existing anti-TB medications to produce derivatives that can function on resistant TB bacilli is one of the potential techniques to overcome drug resistance affordably and straightforwardly. In comparison to novel pharmaceuticals for drug research and progress, these may have a better half-life and greater bioavailability, be more efficient, and serve as inexpensive alternatives. Mycobacterium tuberculosis, which is drugsusceptible or drug-resistant, is effectively treated by several already prescribed medications and their derivatives. Due to this, the current review attempts to give a brief overview of the rifampicin derivatives that can overcome the parent drug's resistance and could, hence, act as useful substitutes. It has been found that one-third of the global population is affected by M. tuberculosis. The most common cause of infection-related death can range from latent TB to TB illness. Antibiotics in the rifamycin class, including rifampicin or rifampin (RIF), rifapentine (RPT), and others, have a special sterilizing effect on M. tuberculosis. We examine research focused on evaluating the safety, effectiveness, pharmacokinetics, pharmacodynamics, risk of medication interactions, and other characteristics of RIF analogs. Drug interactions are especially difficult with RIF because it must be taken every day for four months to treat latent TB infection. RIF continues to be the gold standard of treatment for drug-sensitive TB illness. RIF's safety profile is well known, and the two medicines' adverse reactions have varying degrees of frequency. The authorized once-weekly RPT regimen is insufficient, but greater dosages of either medication may reduce the amount of time needed to treat TB effectively.

Integrated immunoinformatics and subtractive proteomics approach for multi-epitope vaccine designing to combat S. pneumoniae TIGR4.

Streptococcus pneumoniae is one of the major precarious pathogens accountable for over 1.2 million fatalities annually. The key drivers for pneumococcal vaccine development involve high morbidity and mortality in over one million cases, especially in very young children and the elderly. In this study, immunoinformatics was integrated with subtractive proteomics to find antigenic proteins for designing a multi-epitope vaccine against S. pneumoniae. As prospective vaccine targets, the developed pipeline identified two antigenic proteins, i.e., penicillin-binding protein and ATP synthase subunit. Several immunoinformatics and bioinformatics resources were used to forecast T- and B-cell epitopes from specific proteins. By employing a mixture of five cytotoxic T-cell lymphocytes, six helper T-cell lymphocytes, and seven linear B-cell lymphocyte epitopes, a 392 amino acid-long vaccine was designed. To enhance immune responses, the designed vaccine was coupled with a cholera enterotoxin subunit B adjuvant. The designed vaccine was highly antigenic, non-allergenic, and stable for human usage. The stability of the vaccine with toll-like receptor-4 was evaluated by molecular docking and molecular dynamic simulation. In addition, immunological simulation was performed to test its real-world potency. The vaccine codon was then cloned in silico. Overall, this study paves the way for the development of a multi-epitope S. pneumoniae vaccine under laboratory conditions. Furthermore, the current findings warrant for the experimental validation of the final multi-epitope vaccine construct to demonstrate its immunological reinforcing capability and clinical applicability.

Cyclodextrin nanoparticles in targeted cancer theranostics.

The field of cancer nanotheranostics is rapidly evolving, with cyclodextrin (CD)-based nanoparticles emerging as a promising tool. CDs, serving as nanocarriers, have higher adaptability and demonstrate immense potential in delivering powerful anti-cancer drugs, leading to promising and specific therapeutic outcomes for combating various types of cancer. The unique characteristics of CDs, combined with innovative nanocomplex creation techniques such as encapsulation, enable the development of potential theranostic treatments. The review here focuses mainly on the different techniques administered for effective nanotheranostics applications of CD-associated complex compounds in the domain of cancer treatments. The experimentations on various loaded drugs and their complex conjugates with CDs prove effective in in vivo results. Various cancers can have potential nanotheranostics cures using CDs as nanoparticles along with a highly efficient process of nanocomplex development and a drug delivery system. In conclusion, nanotheranostics holds immense potential for targeted drug delivery and improved therapeutic outcomes, offering a promising avenue for revolutionizing cancer treatments through continuous research and innovative approaches.

Culturally adapted psychosocial interventions (CaPSI) for early psychosis in a low-resource setting: study protocol for a large multi-center RCT.

BACKGROUND: Psychosis treatment guidelines recommend cognitive behaviour therapy (CBT) and family intervention (FI), for all patients with first episode psychosis (FEP), though guidance borrows heavily from literature in adults from high income countries. To our knowledge, there are few randomized controlled trials (RCTs) examining the comparative effect of these commonly endorsed psychosocial interventions in individuals with early psychosis from high-income countries and no such trials from low and middle-income countries (LMICs). The present study aims to confirm the clinical-efficacy and cost-effectiveness of delivering culturally adapted CBT (CaCBT) and culturally adapted FI (CulFI) to individuals with FEP in Pakistan. METHOD: A multi-centre, three-arm RCT of CaCBT, CulFI, and treatment as usual (TAU) for individuals with FEP (n = 390), recruited from major centres across Pakistan. Reducing overall symptoms of FEP will be the primary outcome. Additional aims will include improving patient and carer outcomes and estimating the economic impact of delivering culturally appropriate psychosocial interventions in low-resource settings. This trial will assess the clinical-efficacy and cost-effectiveness of CaCBT and CulFI compared with TAU in improving patient (positive and negative symptoms of psychosis, general psychopathology, depressive symptoms, quality of life, cognition, general functioning, and insight) and carer related outcomes (carer experience, wellbeing, illness attitudes and symptoms of depression and anxiety). CONCLUSIONS: A successful trial may inform the rapid scale up of these interventions not only in Pakistan but other low-resource settings, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority groups with FEP. TRIAL REGISTRATION: NCT05814913.

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.

Differential differentiation of B cell lymphopoiesis in lethal and non-lethal murine malaria models.

B cells in protection against malaria and need of experiencing many episodes in humans to achieve a state of immunity is largely unknown. The cellular basis of such defects in terms of B cell generation, maturation and trafficking was studied by taking Plasmodium chabaudi, a non-lethal and Plasmodium berghei, a lethal murine model. A flow cytometry (FCF) based evaluation was used to study alterations in generation and maintenance of B cells in patients with Plasmodium falciparum malaria as well as in murine malaria models. A significant accumulation of mature B cells in bone marrow and immature B cells in circulation was a feature observed only in lethal malaria. At peak parasitaemia, both the models induce a significant decrease in T2 (transitional) B cells with expansion of T1B cells. Studies in patients with acute Pf malaria showed a significant expansion of memory B cells and TB cells with a concomitant decrease in naive2 B cells as compared with healthy controls. This study clearly demonstrates that acute malarial infection induces major disturbances in B cell development in lymphoid organs and trafficking in periphery.

Palliative Role of Zamzam Water against Cyclosporine-Induced Nephrotoxicity through Modulating Autophagy and Apoptosis Crosstalk.

Cyclosporine (CsA) is considered one of the main components of treatment protocols for organ transplantation owing to its immunosuppressive effect. However, its use is very restricted due to its nephrotoxic effect. ZW is an alkaline fluid rich in various trace elements and has a great ability to stimulate antioxidant processes. This study aimed to investigate the possible mitigating effect of ZW on CsA-induced nephrotoxicity and its underlying mechanisms. Forty rats were allocated into four groups (n = 10): a control group, ZW group, cyclosporine A group (injected subcutaneously (SC) with CsA (20 mg/kg/day)), and cyclosporine A+ Zamzam water group (administered CsA (SC) and ZW as their only drinking water (100 mL/cage/day) for 21 days). Exposure to CsA significantly (p < 0.001) increased the serum creatinine level, lipid peroxidation marker level (malondialdehyde; MDA), and the expression of apoptotic markers procaspase-8, caspase-8, caspase- 9, calpain, cytochrome c, caspas-3, P62, and mTOR in renal tissues. Meanwhile, it markedly decreased (p< 0.001) the autophagic markers (AMPK, ULK-I, ATag5, LC3, and Beclin-1), antiapoptotic Bcl-2, and antioxidant enzymes. Moreover, the administration of CsA caused histological alterations in renal tissues. ZW significantly (p < 0.001) reversed all the changes caused by CsA and conclusively achieved a positive outcome in restraining CsA-induced nephrotoxicity, as indicated by the restoration of the histological architecture, improvement of renal function, inhibition of apoptosis, and enhancement of autophagy via the AMPK/mTOR pathway.

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.

Effects of aluminum chloride and coenzyme Q10 on the molecular structure of lipids and the morphology of the brain hippocampus cells.

Aluminum chloride (AlCl3) is a neurotoxic substance, while coenzyme Q10 (CoQ10) is considered a lipid antioxidant. Herein, their effects on the molecular structure of lipids and the morphology of the hippocampus brain tissue were investigated. Three groups of Wistar albino male rats were used in this study. For four weeks, one group was kept as a control group; the second group was given AlCl3; the third group was given AlCl3/CoQ10. Fourier transform infrared (FTIR) and histopathological examinations were utilized to estimate alterations in the molecular structure of the lipids and the cell morphology, respectively. The FTIR spectra revealed considerable decreases in the CH contents and alterations in the molecular ratios of olefinic[double bond, length as m-dash]CH/νas(CH3), νas(CH2)/νas(CH3), and νas(CH2)/[νas(CH2) + νs(CH2)] in the group given AlCl3. However, no significant changes were detected in those rats given AlCl3/CoQ10. Histopathology images uncovered shrinking and dark centers in the pyramidal cells of brain tissue hippocampal cells. The diameters of the pyramidal cells were estimated to be 4.81 ± 0.55 µm, 4.04 ± 0.71 µm, and 4.63 ± 0.71 µm for the control, AlCl3, and AlCl3/CoQ10 groups, respectively. The study showed that the AlCl3 could cause a shrinking of around 16% in the hippocampus pyramidal cells; besides, CoQ10 is a powerful therapeutic antioxidant to help restore the hippocampal neurons to a regular state.

Correction: Effects of aluminum chloride and coenzyme Q10 on the molecular structure of lipids and the morphology of the brain hippocampus cells.

[This corrects the article DOI: 10.1039/D1RA03786B.].

Evidence of patient beliefs, values, and preferences is not provided in osteoporosis clinical practice guidelines.

We examined how patient beliefs, values, and preferences (BVPs) were included and conceptualized in international osteoporosis guidelines. The majority of guidelines did not mention BVPs. When mentioned, BVPs were conceptualized as preference for one medication over another. A broader conceptualization and inclusion of BVPs should be incorporated in osteoporosis guidelines. INTRODUCTION: Our objectives were to determine (1) the extent to which osteoporosis guidelines reflected patients' beliefs, values, and preferences (BVPs); (2) how BVPs were conceptualized; and (3) the methods used to elicit BVPs in the references cited by the guidelines. METHODS: We conducted a document analysis of English-language international osteoporosis guidelines based on the International Osteoporosis Foundation website. We examined each guideline and extracted all instances of statements pertaining to BVPs. The statements were reviewed by two independent researchers. Discrepancies in data extraction were resolved by the first author. We developed categories based on five common elements that represented the BVP statements. RESULTS: Twenty-seven of 70 (39%) guidelines included 95 statements about patient BVPs. Of the 95 statements, 32 statements (14 guidelines) were classified under BVP related to the choice of pharmacotherapy or general treatment, 10 (7 guidelines) under BVP related to adherence to pharmacotherapy or treatment in general, 5 (5 guidelines) under BVP related to financial costs and benefits, 43 (19 guidelines) under other BVP mentioned but not supported by a reference to a primary study or systematic review, and 5 (3 guidelines) under other BVP mentioned and supported by at least one reference to a primary study or systematic review. Twenty-nine references were cited to reflect the BVPs mentioned, including an editorial and quantitative studies. CONCLUSIONS: Twenty-seven (39%) of the guidelines included mention of patients' BVPs. In 19 guidelines, the importance of BVPs was mentioned but these statements were not supported by references to a primary study or systematic review. BVPs were most often (14 guidelines) conceptualized as preference for one medication over another. We suggest that qualitative data be included as evidence of BVPs in guidelines.

Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families.

Approximately 1% of the global population is affected by intellectual disability (ID), and the majority receive no molecular diagnosis. Previous studies have indicated high levels of genetic heterogeneity, with estimates of more than 2500 autosomal ID genes, the majority of which are autosomal recessive (AR). Here, we combined microarray genotyping, homozygosity-by-descent (HBD) mapping, copy number variation (CNV) analysis, and whole exome sequencing (WES) to identify disease genes/mutations in 192 multiplex Pakistani and Iranian consanguineous families with non-syndromic ID. We identified definite or candidate mutations (or CNVs) in 51% of families in 72 different genes, including 26 not previously reported for ARID. The new ARID genes include nine with loss-of-function mutations (ABI2, MAPK8, MPDZ, PIDD1, SLAIN1, TBC1D23, TRAPPC6B, UBA7 and USP44), and missense mutations include the first reports of variants in BDNF or TET1 associated with ID. The genes identified also showed overlap with de novo gene sets for other neuropsychiatric disorders. Transcriptional studies showed prominent expression in the prenatal brain. The high yield of AR mutations for ID indicated that this approach has excellent clinical potential and should inform clinical diagnostics, including clinical whole exome and genome sequencing, for populations in which consanguinity is common. As with other AR disorders, the relevance will also apply to outbred populations.