Plant-Derived Natural Compounds as an Emerging Antiviral in Combating COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a human virus that burst at Wuhan in China and spread quickly over the world, leading to millions of deaths globally. The journey of this deadly virus to different mutant strains is still ongoing. The plethora of drugs and vaccines have been tested to cope up this pandemic. The herbal plants and different spices have received great attention during pandemic, because of their anti-inflammatory, and immunomodulatory properties in treating viruses and their symptoms. Also, it has been shown that nano-formulation of phytochemicals has potential therapeutic effect against COVID-19. Furthermore, the plant derived compound nano-formulation specifically increases its antiviral property by enhancing its bioavailability, solubility, and target-specific delivery system. This review highlights the potentiality of herbal plants and their phytochemical against SARS-CoV-2 utilizing different mechanisms such as blocking the ACE-2 receptors, inhibiting the main proteases, binding spike proteins and reducing the cytokine storms.

Natural history, spectrum and outcome of stage 3 AKI in patients with acute-on-chronic liver failure.

BACKGROUND AND AIM: There is limited data on natural course and interventions in stage-3 acute kidney injury (AKI-3) in patients with acute-on-chronic liver failure (ACLF). We studied the factors of AKI-3 reversal and outcomes of dialysis in ACLF patients. METHODS: Consecutive patients with ACLF were prospectively enrolled (n = 1022) and variables determining AKI and its outcomes were analysed. RESULTS: At 1 month, 337 (33%) patients had AKI-3, of which, 131 had AKI-3 at enrolment and 206 developed AKI-3 during hospital stay. Of patients with AKI-3 at enrolment, 18% showed terlipressin response, 21% had AKI resolution and 59% required dialysis. High MELD (≥35) (model 1), serum bilirubin (≥23 mg/dL) (model 2) and AARC score (≥11) (model 3) were independent risk factors for dialysis. Dialysis was associated with worse survival in all AKI patients but improved outcomes in patients with AKI-3 (p = .022, HR 0.69 [0.50-0.95]). Post-mortem kidney biopsies (n = 61) revealed cholemic nephropathy (CN) in 54%, acute tubular necrosis (ATN) in 31%, and a combination (CN and ATN) in 15%. Serum bilirubin was significantly higher in patients with CN, CN and ATN compared with ATN respectively ([30.8 ± 12.2] vs. [26.7 ± 12.0] vs. [18.5 ± 9.8]; p = .002). CONCLUSION: AKI-3 rapidly increases from 13% to 33% within 30 days in ACLF patients. Histopathological data suggested cholemic nephropathy as the predominant cause which correlated with high bilirubin levels. AKI-3 resolves in only one in five patients. Patients with AARC grade 3 and MELD >35 demand need for early dialysis in AKI-3 for improved outcomes.

Continuing arteriovenous fistula creation by nephrologist and its outcome during COVID pandemic-Analysis of 376 cases.

There has been a significant reduction of elective surgeries including creation of arteriovenous fistulas (AVF) during the ongoing pandemic by the surgeons. Here, we report the retrospective observational data of AVF creation by nephrologists in a single center, during a period of 8 months. A total of 376 fistulae were created in 310 patients. Patients were followed up at 2, 6, and 12 weeks. Twenty-eight patients required fistula creation twice, 16 patients thrice, and two patients underwent fistula creation four times. Of the total, 259 (68.8%) fistulae were radio-cephalic while 99 (26.3%) and 18 (4.79%) were brachio-cephalic and brachio-basilic, respectively. A total of 207 (67%) patients were already on hemodialysis whereas 103 (33%) were planned for elective initiation after fistula maturation. Of the 211 (69%) patients who completed 3 months of follow-up, 31 (15%) expired and 7 (3.3%) were lost to follow-up. Primary failure was observed in 70 (33.2%) fistulae. Fifteen (7.1%) patients were noted to be COVID positive during the follow-up. A total of 279 (90%) patients were alive at last follow-up. Amongst 20 dialysis staffs with 10 nephrologists, only two have developed COVID. Both were having mild illness and recovered completely. This study demonstrates that AVF creation can be performed safely with careful screening and by using adequate personal protective equipment.

Infant birth outcomes are associated with DNA damage biomarkers as measured by the cytokinesis block micronucleus cytome assay: the DADHI study.

Accumulation of DNA damage in the first 1000 days may increase risk of accelerated ageing and degenerative diseases in adult life such as cancers. The extent of DNA damage in infants and the correlation of maternal factors during pregnancy with neonate birth outcomes and DNA damage is not known in infants born in Australia. Therefore, we performed a prospective cohort study to collect data on DNA damage in lymphocytes of Australian infants (aged 0, 3 and 6 months), using the cytokinesis block micronucleus cytome (CBMN-Cyt) assay. The study also explored correlation of CBMN-Cyt biomarkers with infant birth outcomes and maternal anthropometric and lifestyle variables. Peripheral blood lymphocytes were isolated from the infants at birth (cord blood) (n = 82), 3 months (n = 64) and 6 months (n = 53) after birth. DNA damage biomarkers measured ex vivo in binucleated lymphocytes (BNC) included: micronuclei (MN), nucleoplasmic bridges (NPB) and nuclear buds (NBUD). Apoptotic and necrotic lymphocytes were also scored and nuclear division index (NDI) was measured using the frequency of mono-, bi- and multinucleated lymphocyte. MN and NBUD were also scored in mononucleated lymphocytes (MNC). The mean (± SD) frequency of MN, NPB and NBUD in BNCs at birth was 2.0 (± 1.2), 5.8 (± 3.7) and 11.1 (± 5.7) per 1000 BNC, respectively, and tended to decrease significantly at 3 months (P < 0.01, P < 0.0001, P < 0.001, respectively) and 6 months (P < 0.05, P < 0.0001, P < 0.0001, respectively) after birth relative to cord blood when compared with the same cohort of infants (n = 48 at birth, 48 at 3 months and 39 at 6 months). None of the CBMN cytome biomarkers measured at birth was associated with maternal smoking status, alcohol and folic acid intake during pregnancy. The mean gestation age correlated positively with MN (r = 0.38, P = 0.006), NPB (r = 0.30, P = 0.03) and negatively with NDI (r = -0.29, P = 0.03). Infant birth weight associated positively with MN, NPB and NBUD in cord blood (r = 0.24, P = 0.08; r = 0.32, P = 0.02; r = 0.28, P = 0.04, respectively), birth length associated positively with NPB (r = 0.32, P = 0.02) and NBUD (r = 0.27, P = 0.04) while head circumference associated negatively with apoptotic cells (r = -0.27, P = 0.06). APGAR score at 1 and 5 min after birth associated positively with NDI at birth (r = 0.3, P = 0.05, r = 0.28, P = 0.06, respectively). Mother's weight and body mass index (BMI) recorded at the time of recruitment associated positively with NPB (r = 0.38, P = 0.006, r = 0.32, P = 0.02, respectively) and negatively with APGAR score at 5 min (r = -0.25, P = 0.07). The significant positive associations of infant birth weight and length and maternal BMI with CBMN-Cyt biomarkers suggest the possibility of a genotoxic effect of metabolic processes that promote excessive growth and high BMI.

Investigating the Therapeutic Property of Galium verum L. (GV) for MSG induced Audiogenic Epilepsy (AEs) and Neuroprotection through In-Silico and In-Vitro Analysis.

BACKGROUND: Audiogenic Epilepsy (AEs) is a subtype of epileptic seizure that is generally caused by high-intensity sounds. A large number of traditional medicines has been explored in this lieu where our study chased Galium verum L. (Rubiaceae), an herbal plant which is commonly known as Lady's Bedstraw, that contains a highly rich chemical composition including flavonoids (Hispidulin, Quercetin, and Kaempferol), and phenolic acids (chlorogenic acid, caftaric acid, and gallic acid). G verum is well known for its antioxidant, neuroprotective, and anti-inflammatory properties. Recently, the unique role of Adhesion G Protein- Coupled Receptor V1 (ADGRV1) protein in the progression of audiogenic epilepsy has been explored. AIM AND OBJECTIVES: This study aimed to examine the potent phytoconstituents of the hydroalcoholic extract of G. verum L. (HEGV) using analytical techniques. Additionally, our study sought to evaluate the antioxidant, neuroprotective, anti-inflammatory properties, and antiepileptic potency of HEGV by targeting ADGRV1 via in silico and in vitro analyses using SHSY5Y cells. METHOD: HPLC and LC-MS techniques were employed to identify the flavonoids, iridoids, and phenolic acid derivatives present in HEGV. DPPH (2,2-diphenyl-1-picrylhydrazyl), nitric oxide (NO), and hydroxyl (OH) radical scavenging assays were performed to confirm the antioxidant potential of the extract. Additionally, in silico molecular docking and molecular dynamic studies were performed using AutoDock Vina software to analyze the possible interactions between crucial phytoconstituents of HEGV and ADGRV1, followed by cell line analysis. In the in vitro analysis, antioxidant, neuroprotective, and anti-inflammatory properties were assessed via cell viability assay, IL, GABA, and glutamate estimation. RESULTS: LC-MS and HPLC analyses revealed high concentrations of hispidulin, a major flavonoid found in HEGV. HEGV exhibited moderate-to-high free radical-scavenging activities comparable to those of ascorbic acid. Docking analysis demonstrated that hispidulin has a stronger binding affinity with ADGRV1 (Vina score = -8.6 kcal/mol) than other compounds. Furthermore, cell line analysis revealed that the MSG exacerbates the neurodegeneration and neuroinflammation, whereas, HEGV and Hispidulin both possess neuroprotective, antioxidant, and antiepileptic activities. CONCLUSION: HEGV and Hispidulin proved to be promising candidates for treating audiogenic epilepsy by modulating ADGRV1.

A rare case of Fanconi anemia with Mitomycin C sensitivity: A pediatrics case report.

Key Clinical Message: Fanconi anemia with Mitomycin C sensitivity is a rare, complex hematological condition. Our case study emphasizes the significance of early diagnosis, appropriate genetic testing, and cautious use of chemotherapeutic agents. Abstract: Fanconi anemia (FA) is a rare genetic disorder characterized by bone marrow failure, congenital anomalies, and predisposition to cancer. Here, we present the case of a 6-year-old boy with a known diagnosis of Fanconi anemia who exhibited sensitivity to Mitomycin C. The patient had a history of recurrent blood transfusions due to anemia and was referred to our institution following worsening symptoms, including pallor, swelling in limbs, and respiratory distress. Physical examination revealed characteristic features of FA such as mesomelia, low-set ears, hyperpigmented macules, microcephaly, micropthalmos, and thumb hypoplasia. Imaging studies demonstrated bilateral radial hypoplasia and congenital agenesis of the left kidney. Laboratory investigations revealed pancytopenia, aberrant liver function tests, and elevated inflammatory markers. Importantly, the patient exhibited sensitivity to Mitomycin C, highlighting the necessity for caution in selecting chemotherapeutic agents in FA patients. This case underscores the importance of early recognition, comprehensive evaluation, and tailored management strategies of patients with Fanconi anemia to optimize outcomes and minimize complications.

Tackling municipal solid waste crisis in India: Insights into cutting-edge technologies and risk assessment.

Municipal Solid Waste (MSW) management is a pressing global concern, with increasing interest in Waste-to-Energy Technologies (WTE-T) to divert waste from landfills. However, WTE-T adoption is hindered by financial uncertainties. The economic benefits of MSW treatment and energy generation must be balanced against environmental impact. Integrating cutting-edge technologies like Artificial Intelligence (AI) can enhance MSW management strategies and facilitate WTE-T adoption. This review paper explores waste classification, generation, and disposal methods, emphasizing public awareness to reduce waste. It discusses AI's role in waste management, including route optimization, waste composition forecasting, and process parameter optimization for energy generation. Various energy production techniques from MSW, such as high-solids anaerobic digestion, torrefaction, plasma pyrolysis, incineration, gasification, biodegradation, and hydrothermal carbonization, are examined for their advantages and challenges. The paper emphasizes risk assessment in MSW management, covering chemical, mechanical, biological, and health-related risks, aiming to identify and mitigate potential adverse effects. Electronic waste (E-waste) impact on human health and the environment is thoroughly discussed, highlighting the release of hazardous substances and their contribution to air, soil, and water pollution. The paper advocates for circular economy (CE) principles and waste-to-energy solutions to achieve sustainable waste management. It also addresses complexities and constraints faced by developing nations and proposes strategies to overcome them. In conclusion, this comprehensive review underscores the importance of risk assessment, the potential of AI and waste-to-energy solutions, and the need for sustainable waste management to safeguard public health and the environment.

Limonin (LM) and its derivatives: Unveiling the neuroprotective and anti-inflammatory potential of LM and V-A-4 in the management of Alzheimer's disease and Parkinson's disease.

Neuroinflammation and neuronal apoptosis are central pathogenic consequences associated with Alzheimer's Disease (AD) and Parkinson's Disease (PD). Limonin (LM), a tetracyclic triterpenoid available in citrus fruits, has anti-tumor, antioxidant, anti-inflammatory, hepatoprotective, and neuroprotective actions. LM derivative, V-A-4 emerged as a potential neuroprotective drug due to their ability to target multiple molecular pathways intertwined with neuroinflammation and neuronal apoptosis. To date, the treatment of AD and PD is not successful even though the understanding of the mechanism of neuroinflammation and neuronal apoptosis is vast in the literature. Thus, there is an urgent need to identify novel neuroprotective drugs that could target the multiple molecular pathways associated with neuroinflammation and neuronal apoptosis. The various online databases (Google scholar, Pubmed, Scopus) were searched via keywords: limonin, limonin derivatives and neuroprotection. This review highlights the multifunctional nature of LM and derivatives in combating neuroinflammation and neuronal apoptosis by stimulating PI3K/AKT and downregulating TLR4/NF-κB critical pathways. By intervening in the secretion of NO and TNF-α from glial cells, V-A-4 attenuates the damaging cascade of neuroinflammation by suppressing IKK-α and IKK-ß. Furthermore, V-A-4 demonstrates its versatility by suppressing the manifestation of miR-146a and miR-155, both intimately linked to neuroinflammation, this review summarized the activities of LM and its derivatives against AD and PD, with a special focus on V-A-4 as an effective neuroprotective drug. V-A-4's ability to stimulate PI3K/AKT signaling further underscores its neuroprotective effect in combating AD and PD. More in-vitro cell line studies are needed to develop V-A-4 as an upcoming neuroprotective compound.

A rare case of chikungunya encephalitis and its management: A case report and literature review.

Key Clinical Message: Chikungunya encephalitis, though rare, warrants clinical attention due to its severe complications. Early identification and appropriate management are crucial for improved outcomes in patients with this rare manifestation of chikungunya virus (CHIKV) infection. Abstract: CHIKV infection is commonly associated with fever and joint pains, but neurological complications such as encephalitis are rare. Here, we present a unique case of confirmed chikungunya encephalitis in a 12-year-old male exhibiting atypical neurological symptoms. The diagnostic journey involved comprehensive neuroimaging and serological investigations, revealing intriguing findings on magnetic resonance imaging and positive CHIKV RNA in serum and cerebrospinal fluid. We discuss the clinical presentation, radiological characteristics, and management strategies, emphasizing the importance of recognizing this uncommon neurological manifestation of CHIKV infection.

Longitudinal Assessment of Health-Related Quality of Life in Three Different Hyperphosphatemia Management Groups of Stage III and IV Chronic Kidney Disease Patients.

Introduction: Health-related quality of life (HRQoL) has emerged as an important outcome measure inpatients with CKD. The lack of prospective studies on HRQoL and its relation with hyperphosphatemia control measures among pre-dialysis patients necessitated the need for this study. Methods: This is a prospective, randomized, controlled, open-labelled studythat was conducted for one year on 120 CKD stages III and IV patients divided equally into three groups: Group 1, in which patients under went dietary phosphorus modification; Group 2, in which they were administered calcium-based phosphate binders; and Group 3, in which they were administered non-calcium-based phosphate binders. Patients were assessed for HRQoL, fibroblast growth factor 23 (FGF 23), intact parathyroid hormone (iPTH), phosphorus, and nutritional status, and dietary phosphorus control strategies at 0, 6, and 12 months. HRQoL was measured by using the 36-item Short Form Survey (SF-36) that included a physical component score (PCS) and mental component score (MCS). The scores is ranging from 0 to 100. Higher scores indicate better health status. Usingthe two-wayand one-way repeated measure ANOVA, we analyzed equality of group means, time intervals, and interactions. Results: At baseline, the mean PCS and MCS were equal in three groups. PCS improved significantly (P < 0.00) from baseline to one year in all the three groups: ingroup 1, the PCS score was 66.5 ± 13.5to 75.1 ± 9.76; in group 2, it was 68.9 ± 11.80 to 77.2 ± 7.50; and in group 3, it was 66.2 ± 12.16 to 73.8 ± 9.27. Initially, MCS declined substantially on the sixth month but recovered afterone year. Multiple regression analysis in 13 associated parameters yielded R2 of 13.7% and 18.1% in PCS and MCS, respectively, indicating little contribution of various parameters. Conclusion: There has been a significant positive change in PCSs in three hyperphosphatemia management groups over a period of 12 months. Among the three study groups, the incremental changes in PCS and MCS scores were insignificant.

Giant Retinal Astrocytoma: A Case Report of an Uncommon Presentation of Tuberous Sclerosis in a Young Female.

Tuberous sclerosis (TS) is a rare multisystem autosomal dominant genetic disorder with characteristic pathognomonic genetic mutations involving the TSC (tuberous sclerosis complex) group of genes. Ocular signs are fairly common and include an achromic patch and retinal astrocytic hamartomas, which usually have a maximum size of between 0.5 and 5 mm. The incidence of tuberous sclerosis is estimated to be 1 in 5000-10,000 individuals, with both familial and sporadic cases reported. The diagnostic criteria for tuberous sclerosis include the presence of major and/or minor clinical features as well as genetic mutations. We present the case of a 15-year-old girl, presented with a history of seizures and blurred vision. Physical examination revealed angiofibroma on the face. Further evaluation, including contrast-enhanced MRI of the brain and ophthalmological consultation, led to the diagnosis of tuberous sclerosis. Additional imaging studies confirmed the presence of subependymal giant cell astrocytoma, retinal astrocytoma, lymphangioleiomyomatosis in the lungs, and renal angiomyolipoma. This case highlights the importance of considering tuberous sclerosis in patients presenting with seizures and ocular symptoms. This case sheds light on early diagnosis and appropriate management which are crucial in preventing complications and improving patient outcomes.

The significance of uterine artery embolization in the treatment of utero-cervical cancer: A single case report.

Key Clinical Message: Uterine artery embolization demonstrated significant efficacy in the treatment of utero-cervical cancer. This minimally invasive procedure holds promise as a valuable adjunct therapy, potentially offering improved outcomes and reduced morbidity in select cases. Further research is warranted to validate its broader clinical utility. Abstract: Vaginal bleeding is a common complication of Cervical cancer that can be considered a critical emergency. Conventional hemostatic treatments may occasionally help reduce the bleeding but are not an effective long-term solution. Uterine Artery Embolization, a minimally invasive intervention, can halt the bleeding, achieving hemostasis, while removing many of the complications that alternative interventions carry. We outline a case study of a patient with extensive vaginal bleeding who had uterocervical malignancy and talk about the benefits of uterine artery embolisation for therapeutic management.

A rare case of Balo's disease in a young adult: A clinical presentation and management.

Key Clinical Message: Accurate diagnosis of rare neurological conditions like Balo's concentric sclerosis (BCS) is challenging but crucial for tailored treatment. Interdisciplinary collaboration and further research are essential to advance our understanding. Abstract: This case report presents a 32-year-old female patient with a puzzling neurological condition characterized by feverish feelings, joint pain, unclear speech, and an unsteady gait. Initial management did not lead to improvement, and further examination revealed neurological involvement and joint tenderness without signs of inflammatory arthritis. Laboratory investigations ruled out infectious and autoimmune causes. Magnetic resonance imaging (MRI) showed well-defined lesions with concentric rings, leading to a diagnosis of Balo' concentric sclerosis. Treatment with intravenous methylprednisolone resulted in limited improvement. This case highlights the importance of thorough evaluation and collaboration in diagnosing rare neurological conditions. Further research is needed to enhance the understanding and treatment of rare neurological disorders.

Longitudinal Multi-omic Immune Profiling Reveals Age-Related Immune Cell Dynamics in Healthy Adults.

The generation and maintenance of protective immunity is a dynamic interplay between host and environment that is impacted by age. Understanding fundamental changes in the healthy immune system that occur over a lifespan is critical in developing interventions for age-related susceptibility to infections and diseases. Here, we use multi-omic profiling (scRNA-seq, proteomics, flow cytometry) to examined human peripheral immunity in over 300 healthy adults, with 96 young and older adults followed over two years with yearly vaccination. The resulting resource includes scRNA-seq datasets of >16 million PBMCs, interrogating 71 immune cell subsets from our new Immune Health Atlas. This study allows unique insights into the composition and transcriptional state of immune cells at homeostasis, with vaccine perturbation, and across age. We find that T cells specifically accumulate age-related transcriptional changes more than other immune cells, independent from inflammation and chronic perturbation. Moreover, impaired memory B cell responses to vaccination are linked to a Th2-like state shift in older adults' memory CD4 T cells, revealing possible mechanisms of immune dysregulation during healthy human aging. This extensive resource is provided with a suite of exploration tools at https://apps.allenimmunology.org/aifi/insights/dynamics-imm-health-age/ to enhance data accessibility and further the understanding of immune health across age.

The Role of monosodium glutamate (MSG) in Epilepsy and other Neurodegenerative Diseases: Phytochemical-based Therapeutic Approaches and Mechanisms.

Epilepsy is a common neurological disease affecting 50 million individuals worldwide, and some forms of epilepsy do not respond to available treatments. Overactivation of the glutamate pathway and excessive entrance of calcium ions into neurons are proposed as the biochemical mechanisms behind epileptic seizures. However, the overactivation of neurons has also been associated with other neurodegenerative diseases (NDDs), such as Alzheimer's, Parkinson's, Huntington's, and multiple sclerosis. The most widely used food ingredient, monosodium glutamate (MSG), increases the level of free glutamate in the brain, putting humans at risk for NDDs and epilepsy. Glutamate is a key neurotransmitter that activates nerve cells. MSG acts on glutamate receptors, specifically NMDA and AMPA receptors, leading to an imbalance between excitatory glutamate and inhibitory GABA neurotransmission. This imbalance can cause hyperexcitability of neurons and lead to epileptic seizures. Overuse of MSG causes neuronal cells to become overexcited, which in turn leads to an increase in the flow of Ca2+ and Na+ ions, mutations, and upregulation in the enzymes superoxide dismutase 1 (SOD-1) and TDP43, all of which contribute to the development of NDDs. While TDP43 and SOD-1 protect cells from damage, a mutation in their genes makes the proteins unprotective and cause neurodegeneration. Yet to what extent mutant SOD1 and TDP43 aggregates contribute to neurotoxicity is generally unknown. This study is focused on neuroprotective herbal medications that can pass the blood-brain barrier and cure MSG-induced NDDs and the factors that influence MSG-induced glutaminergic, astrocyte, and GABAergic neuron abnormalities causing neurodegeneration.

A Modified Tongue Crib Appliance for Correction of Tongue Thrusting.

Digit sucking and tongue thrusting are parafunctional habits that are commonly observed and are recognized as major etiological factors in the development of dental malocclusion. Treatment for these oral habits typically involves removal of the etiology, retraining exercises, and use of mechanical restraining appliances. A 13-year-old male patient reported a complaint of forwardly placed upper front teeth. The extraoral examination of the patient showed a convex profile, good facial symmetry, acute nasolabial angle, incompetent lips at rest, and a shallow mentolabial sulcus. Intraoral examination showed class I molar and canine relations on either side, a mild open bite tendency, a midline diastema, proclined upper and lower anteriors, an increased overjet, and tongue thrusting habit. A modification to the tongue crib was made by adding an acrylic bead in the center of the crib. The patient was trained to roll the bead posteriorly with the aim of retraining the tongue to posture away from the front teeth. Harmful forces of the tongue can result in excessive posterior teeth eruption, open bite, and increased overjet. Duration of appliance wear and type of appliance used are important considerations in treating patients with tongue thrust or open bite. A modified tongue crib was used for six months resulting in significant improvement in maxillary anterior dentition position, lip competence, arch forms, overbite, and midline diastema closure. A tongue crib is a useful tool for addressing tongue thrusting and digit-sucking behaviors by retraining the related muscles, providing physical restraint, and serving as a reminder to break the habit. It can be used in conjunction with a fixed appliance to improve its effectiveness.

Site-specific analysis reveals candidate cross-kingdom small RNAs, tRNA and rRNA fragments, and signs of fungal RNA phasing in the barley-powdery mildew interaction.

The establishment of host-microbe interactions requires molecular communication between both partners, which may involve the mutual transfer of noncoding small RNAs. Previous evidence suggests that this is also true for powdery mildew disease in barley, which is caused by the fungal pathogen Blumeria hordei. However, previous studies lacked spatial resolution regarding the accumulation of small RNAs upon host infection by B. hordei. Here, we analysed site-specific small RNA repertoires in the context of the barley-B. hordei interaction. To this end, we dissected infected leaves into separate fractions representing different sites that are key to the pathogenic process: epiphytic fungal mycelium, infected plant epidermis, isolated haustoria, a vesicle-enriched fraction from infected epidermis, and extracellular vesicles. Unexpectedly, we discovered enrichment of specific 31-33-base 5'-terminal fragments of barley 5.8S ribosomal RNA in extracellular vesicles and infected epidermis, as well as particular B. hordei transfer RNA fragments in haustoria. We describe canonical small RNAs from both the plant host and the fungal pathogen that may confer cross-kingdom RNA interference activity. Interestingly, we found first evidence of phased small interfering RNAs in B. hordei, a feature usually attributed to plants, which may be associated with the posttranscriptional control of fungal coding genes, pseudogenes, and transposable elements. Our data suggest a key and possibly site-specific role for cross-kingdom RNA interference and noncoding RNA fragments in the host-pathogen communication between B. hordei and its host barley.

Advancing Colorectal Cancer Screening: A Comprehensive Systematic Review of Artificial Intelligence (AI)-Assisted Versus Routine Colonoscopy.

Colorectal cancer (CRC) is a rapidly escalating public health concern, which underlines the significance of its early detection and the need for the refinement of current screening methods. In this systematic review, we aimed to analyze the potential advantages and limitations of artificial intelligence (AI)-based computer-aided detection (CADe) systems as compared to routine colonoscopy. This review begins by shedding light on the global prevalence and mortality rates of CRC, highlighting the urgent need for effective screening techniques and early detection of this cancer type. It addresses the problems associated with undetected adenomas and polyps and the subsequent risk of interval CRC following colonoscopy. The incorporation of AI into diagnostics has been studied, specifically the use of CADe systems which are powered by deep learning. The review summarizes the findings from 13 randomized controlled trials (RCTs) (2019-2023), evaluating the impact of CADe on polyp and adenoma detection. The findings from the studies consistently show that CADe is superior to conventional colonoscopy procedures in terms of adenoma detection rate (ADR) and polyp detection rate (PDR), particularly with regard to small and flat lesions which are easily overlooked. The review acknowledges certain limitations of the included studies, such as potential performance bias and geographic limitations. The review ultimately concludes that AI-assisted colonoscopy can reduce missed lesion rates and improve CRC diagnosis. Collaboration between experts and clinicians is key for successful implementation. In summary, this review analyzes recent RCTs on AI-assisted colonoscopy for polyp and adenoma detection. It describes the likely benefits, limitations, and future implications of AI in enhancing colonoscopy procedures and lowering the incidence of CRC. More double-blinded trials and studies among diverse populations from different countries must be conducted to substantiate and expand upon the findings of this review.

Inflammation in Cardiovascular Disease: A Comprehensive Review of Biomarkers and Therapeutic Targets.

Cardiovascular disorders (CVDs) represent a global challenge and are regarded as one of the leading causes of mortality. The role of inflammation as a risk factor in these disorders has been studied, with the accelerated atherosclerotic process being a crucial factor in the pathogenesis. Several inflammatory biomarkers such as C-reactive protein (CRP), Interleukins (ILs), Tumor Necrosis Factor-alpha (TNF-α), and others have been identified that play a role in the atherosclerotic process, thus linking systemic inflammatory conditions with CVDs, including acute myocardial infarction (AMI), chronic heart failure (CHF), venous thromboembolism (VTE) and others. These markers could be used to predict the risk of CVDs. Understanding the precise mechanisms can lead to therapeutic strategies targeted at pro-inflammatory processes. We aim to provide an overview of the existing literature on the role of inflammation in various cardiovascular disorders and identify different inflammatory biomarkers and therapeutic targets in this comprehensive literature review. We reviewed 190 references published between 2013 and August 3, 2023, in well-reputed journals and analyzed eight selected papers in-depth. We describe the pathophysiologic pathways that lead to atherosclerosis and other cardiovascular pathologies. Several inflammatory cytokines encompassing various groups were identified to be causing endothelial dysfunction, leading to an increased risk for CVDs. Polymorphisms in the genes for different cytokines also led to different levels of susceptibility to CVDs. Nevertheless, future research detailing the inflammatory pathways and their link with CVDs would lead to better outcomes for patients with preexisting and new onset of CVDs as well as chronic inflammatory disorders.