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Chitosan is used in many applications due to its biodegradability, biocompatibility, nontoxicity, nonadhesiveness, and film-forming capabilities. Chitosan has antibacterial and antifungal activities, which are two of its other desirable attributes. However, chitosan can only dissolve in acidic liquids (1-3 % acetic acid), limiting its practical application. The hydroxyl and amino functional groups in the chitosan backbone are essential for chemical modification, which is a viable alternative for overcoming this obstacle. So, N- or O-, and N, O-substituted chitosan may yield derivatives with increased water solubility, biocompatibility, biodegradability, and bio-evaluation. In the same manner, the physicochemical properties of chitosan, including its mechanical and thermal properties, can be improved by cross-linking reactions. This review provides an overview of chitosan, including its origins and their solubility. Also, the review extend and discuss in details most of all chemical reactions that happened on the amino group, hydroxyl group, or both amino group and hydroxyl group to create modified chitosan-based organic materials. Finally, the problems that still need to be solved and probable future areas for study are discussed.

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Burkitt lymphoma is an aggressive B-cell non-Hodgkin lymphoma (NHL). Primary CNS lymphoma (PCNSL) is a rare disease, and the subtype of Burkitt lymphoma presenting as a sole CNS lesion is an even rarer diagnosis. Acute sudden blindness is a rare presenting symptom of PCNSL or NHL in general. We present an interesting case of a four-year-old boy with dysmorphic features whose visual examination showed a sudden bilateral loss of vision. There was bilateral eye proptosis and complete ptosis. Extraocular muscles were fixed straight. The pupils were fixed and mid dilated bilaterally and there was grade 3/4 papilledema in both eyes. Neuroimaging showed a mass in the base of the skull, extending to orbits and sinuses. A cervical biopsy of the enlarged lymph nodes was taken and a histopathological diagnosis of Burkitt lymphoma was made. Genetic analysis showed a GNB1 mutation, and the patient was diagnosed with Kabuki syndrome by a pediatrician, based on characteristic dysmorphic features. Treatment with steroids and chemotherapy was initiated.

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Automatic alerting systems (AASs) can identify adverse health events but emergency communication relies on human operators and natural languages. For complete automation, we need to code the diversity of adverse events in a granularity that supports optimal dispatches. Hence, AAs shall integrate with the International Classification of Diseases (ICD). The ICD-11 coding system includes chapters for external causes of injury. However, ICD-11 supports coding injury incidents in electronic health records (EHRs) after they have occurred, while disregarding integrating real-time injury reporting within its framework. We explore the potential challenges associated with integrating ICD-11 into AAS by analyzing external causes of morbidity or mortality and the dimensions of external causes as potential areas of integration. We recognize the themes: (i) incident of injury, (ii) mode of transport, (iii) indoor location, (iv) outdoor location, and (v) type of building, and identify four challenges: (i) conceptual differences between the two systems, (ii) injury identification, (iii) presence of entities below the shoreline in ICD-11, and (iv) lack of specificity in certain ICD-11 codes related to AASs. For easy integration of ICD-11 into AASs, we recommend an AAS data dictionary and propose ICD-11 updates related to external causes of injury.

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Lung cancer (LC) is a crisis of catastrophic proportions. It is a global problem and urgently requires a solution. The classic chemo drugs are lagging behind as they lack selectivity, where their side effects are spilled all over the body, and these adverse effects would be terribly tragic for LC patients. Therefore, they could make a bad situation worse, inflict damage on normal cells, and inflict pain on patients. Since our confidence in classic drugs is eroding, chitosan can offer a major leap forward in LC therapy. It can provide the backbone and the vehicle that enable chemo drugs to penetrate the hard shell of LC. It could be functionalized in a variety of ways to deliver a deadly payload of toxins to kill the bad guys. It is implemented in formulation of polymeric NPs, lipidic NPs, nanocomposites, multiwalled carbon nanotubes, and phototherapeutic agents. This review is a pretty clear proof of chitosan's utility as a weapon in battling LC. Chitosan-based formulations could work effectively to kill LC cells. If a researcher is looking for a vehicle for medication for LC therapy, chitosan can be an appropriate choice.

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Lignans are biologically active compounds widely distributed, recognized, and identified in seeds, fruits, and vegetables. Lignans have several intriguing bioactivities, including anti-inflammatory, antioxidant, and anticancer activities. Nrf2 controls the expression of many cytoprotective genes. Activation of Nrf2 is a promising therapeutic approach for treating and preventing diseases resulting from oxidative injury and inflammation. Lignans have been demonstrated to stimulate Nrf2 signaling in a variety of in vitro and experimental animal models. The review summarizes the findings of fourteen lignans (Schisandrin A, Schisandrin B, Schisandrian C, Magnolol, Honokiol, Sesamin, Sesamol, Sauchinone, Pinoresinol, Phyllanthin, Nectandrin B, Isoeucommin A, Arctigenin, Lariciresinol) as antioxidative and anti-inflammatory agents, affirming how Nrf2 activation affects their pharmacological effects. Therefore, lignans may offer therapeutic candidates for the treatment and prevention of various diseases and may contribute to the development of effective Nrf2 modulators.

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Liver cancer (LC) is the sixth most common disease and the third most common cause of cancer-related mortality. The WHO predicts that more than 1 million deaths will occur from LC by 2030. Hepatocellular carcinoma (HCC) is a common form of primary LC. Today, the management of LC involves multiple disciplines, and multimodal therapy is typically selected on an individual basis, considering the intricate interactions between the patient's overall health, the stage of the tumor, and the degree of underlying liver disease. Currently, the treatment of cancers, including LC, has undergone a paradigm shift in the last ten years because of immuno-oncology. To treat HCC, immune therapy approaches have been developed to enhance or cause the body's natural immune response to specifically target tumor cells. In this context, immune checkpoint pathway inhibitors, engineered cytokines, adoptive cell therapy, immune cells modified with chimeric antigen receptors, and therapeutic cancer vaccines have advanced to clinical trials and offered new hope to cancer patients. The outcomes of these treatments are encouraging. Additionally, treatment using stem cells is a new approach for restoring deteriorated tissues because of their strong differentiation potential and capacity to release cytokines that encourage cell division and the formation of blood vessels. Although there is no proof that stem cell therapy works for many types of cancer, preclinical research on stem cells has shown promise in treating HCC. This review provides a recent update regarding the impact of immunotherapy and stem cells in HCC and promising outcomes.

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This paper presents a super wideband and high-gain log periodic dipole array (LPDA) antenna. The overall structure of the antenna was constructed using microwave studio computer simulation technology. The optimal sizes of the planned antenna are 39 × 10× 0.254 mm3. The engineered antenna arrangement is implemented on an RT5880 substrate as a dielectric medium. The LPDA is arranged in four arms that are equally spaced on both lines. The main 50Ω feeder line is partially grounded at the back of the substrate. A combination of circular director units is being studied and tuned in a regular pattern at a predefined distance from the antenna. An improvement in gain of 3 dBi is the response of the director units. The Conformist LPDA is adjusted to achieve a wide range of millimeter wave bands ranging from 40 to over 70 GHz. The antenna resonates at 60 GHz, where the maximum realized gain of 14.97 dBi is attained. The antenna was tested for utilization in the V-band involving wireless personal area network (WPAN) applications recommended by IEEE 802.11ad and IEEE 802.15.3c. The outcomes of the constructed antenna elements' tests and simulations agree fairly well. The proposed layout works better than previous efforts in this field.

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BACKGROUND AND AIMS: Acute kidney injury (AKI) due to renal ischemia-reperfusion injury (RIRI) is associated with high morbidity and mortality, with no renoprotective drug available. Previous research focused on single drug targets, yet this approach has not reached translational success. Given the complexity of this condition, we aimed to identify a disease module and apply a multitarget network pharmacology approach. METHODS: Identification of a disease module with potential drug targets was performed utilizing Disease Module Detection algorithm using NADPH oxidases (NOXs) as seeds. We then assessed the protective effect of a multitarget network pharmacology targeting the identified module in a rat model of RIRI. Rats were divided into five groups; sham, RIRI, and RIRI treated with setanaxib (NOX inhibitor, 10 mg/kg), etanercept (TNF-α inhibitor, 10 mg/kg), and setanaxib and etanercept (5 mg/kg each). Kidney functions, histopathological changes and oxidative stress markers (MDA and reduced GSH) were assessed. Immunohistochemistry of inflammatory (TNF-α, NF-κB) apoptotic (cCasp-3, Bax/Bcl 2), fibrotic (α-SMA) and proteolysis (MMP-9) markers was performed. RESULTS: Our in-silico analysis yielded a disease module with TNF receptor 1 (TNFR1A) as the closest target to both NOX1 and NOX2. Targeting this module by a low-dose combination of setanaxib, and etanercept, resulted in a synergistic effect and ameliorated ischemic AKI in rats. This was evidenced by improved kidney function and reduced expression of inflammatory, apoptotic, proteolytic and fibrotic markers. CONCLUSIONS: Our findings show that applying a multitarget network pharmacology approach allows synergistic renoprotective effect in ischemic AKI and might pave the way towards translational success.

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Unroofed coronary sinus (UCS) represents a rare subtype of atrial septal defect (ASD), an adult congenital heart disease characterized by communication between the systemic and pulmonary circulations at the atrial level. This case report presents the unique occurrence of a large, unrepaired ASD secundum and an incidentally identified UCS type II in a 25-year-old female during a cardiac murmur assessment. The diagnosis of ASD secundum was initially made using transthoracic echocardiography (TTE) and was later confirmed with a transesophageal echocardiogram. The identification of the UCS was achieved through the utilization of cardiac computed tomography angiography (CCTA). Ultimately, the patient underwent a successful reroofing procedure using a bovine pericardial patch.

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BACKGROUND: Diabetes mellitus and depression are serious common diseases, and the number of people with both conditions is rising steadily. Depression in people with diabetes mellitus results in poorer prognosis through different mechanisms. On the other hand, the presence of diabetes in individuals with depression increases functional impairment that is associated with depression. AIMS: The study aimed to assess the prevalence and factors associated with depression among adults with type 2 diabetes mellitus attending a diabetes clinic in Cairo, Egypt. METHODS: A cross-sectional study was conducted among adult patients with diabetes type 2 attending a diabetes clinic in the endocrinology department in Ain Shams University Teaching Hospital, Cairo, Egypt. Data were collected through face-to-face interviews by trained psychiatrists and from patients' records. RESULTS: The prevalence of depression among diabetic patients was 21.8% (95% CI [15.6%, 29.1%]). Depression was more common among younger age groups and those with a higher level of education. There was no significant difference between those with lifetime depression compared to those without depression regarding physical health complications. CONCLUSIONS: The prevalence of depression among patients with type 2 diabetes is high. Given the impact of co-morbid diabetes and depression, diabetic patients should be routinely screened for the latter condition.

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BACKGROUND: The incidence of diabetes mellitus (DM) is dramatically increasing worldwide, and it is expected to affect 700 million cases by 2045. Diabetes influences health care economics, human quality of life, morbidity, and mortality, which were primarily seen extensively in developing countries. Uncontrolled DM, which results in consistent hyperglycemia, may lead to severe life-threatening complications such as nephropathy, retinopathy, neuropathy, and cardiovascular complications. METHODOLOGY: In addition to traditional therapies with insulin and oral anti-diabetics, researchers have developed new approaches for treatment, including stem cell (SC) therapy, which exhibits promising outcomes. Besides its significant role in treating type one DM (T1DM) and type two DM (T2DM), it can also attenuate diabetic complications. Furthermore, the development of insulin-producing cells can be achieved by using the different types of SCs, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and multiple types of adult stem cells, such as pancreatic, hepatic, and mesenchymal stem cells (MSC). All these types have been extensively studied and proved their ability to develop insulin-producing cells, but every type has limitations. CONCLUSION: This review aims to enlighten researchers about recent advances in stem cell research and their potential benefits in DM and diabetic complications.

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This scientific review documents the recent progress of C3-spirooxindoles chemistry (synthesis and reaction mechanism) and their bioactivities, focusing on the promising results as well as highlighting the biological mechanism via the reported molecular docking findings of the most bioactive derivatives. C3-Spirooxindoles are attractive bioactive agents and have been found in a variety of natural compounds, including alkaloids. They are widely investigated in the field of medicinal chemistry and play a key role in medication development, such as antivirals, anticancer agents, antimicrobials, etc. Regarding organic synthesis, several traditional and advanced strategies have been reported, particularly those that started with isatin derivatives.

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Studies focusing on natural products have been conducted worldwide, and the results suggest that their natural ingredients effectively treat a wide range of illnesses. Baicalin (BIA) is a glycoside derived from the flavonoid baicalein present in Scutellaria baicalensis of the Lamiaceae family. Interestingly, BIA has been shown to protect the lungs in several animal models used in numerous studies. Therefore, we fully analyzed the data of the studies that focused on BIA's lung protective function against various injuries and included them in this review. Interestingly, BIA exhibits promising effects against acute lung injury, lung fibrosis, pulmonary embolism, and lung remodelling associated with COPD, LPS, and paraquat insecticide. BAI exhibits anticancer activity against lung cancer. Additionally, BIA potently attenuates lung damage associated with infections. BIA primarily exerts its therapeutic effects by suppressing inflammation, oxidative stress immune response, and apoptosis pathways. Nrf2/HO-1, PI3K/Akt, NF-κB, STAT3, MAPKs, TLR4, and NLRP3 are important targets in the pulmonary therapeutic effects of BIA on different lung disease models. Consequently, we recommend using it in future potential clinical applications, its contribution to treatment guidelines, and translating its promising effects to clinical practice in lung diseases.

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Necroptosis, a type of programmed cell death that resembles necrosis, is now known to depend on a different molecular mechanism from apoptosis, according to several recent studies. Many efforts have reported the possible influence of necroptosis in human disorders and concluded the crucial role in the pathophysiology of various diseases, including liver diseases, renal injuries, cancers, and others. Fibrosis is the most common end-stage pathological cascade of several chronic inflammatory disorders. In this review, we explain the impact of necroptosis and fibrosis, for which necroptosis has been demonstrated to be a contributing factor. We also go over the inhibitors of necroptosis and how they have been applied to fibrosis models. This review helps to clarify the role of necroptosis in fibrosis and will encourage clinical efforts to target this pathway of programmed cell death.

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BACKGROUND: Dexamethasone-induced neurotoxicity has been previously reported. However, the molecular mechanisms are still not completely understood. OBJECTIVES: The current work aimed to investigate the modulatory effects of α- and ß-adrenergic receptors on dexamethasone-induced neurotoxicity in rats focused on changes in ß-arrestin2 and molecular markers of neural injury in cerebral cortex. METHODS: Male Wistar rats were subcutaneously injected with dexamethasone (10 mg/kg/day) for 7 days to induce neural injury in the cerebral cortex. The experiment involved 5 groups: control, dexamethasone, carvedilol, propranolol, and doxazosin. In the last 3 groups, drugs were given 2 hours before dexamethasone injection. At the end of experiment, brain samples were collected for measurement of brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), kinase activity of protein kinase B (Akt), diacylglycerol (DAG), α-smooth muscle actin (α-SMA), Smad3, ß-amyloid and phospho-tau protein levels in addition to histopathological examination of brain tissue using hematoxylin-eosin, Nissl, and Sirius red stains. Moreover, ß-arrestin2 levels in the cerebral cortex were measured using immunohistochemical examination. RESULTS: Dexamethasone slightly reduced brain weight and significantly decreased BDNF, Akt kinase activity and ß-arrestin2 but markedly induced degeneration of cortical neurons and significantly increased GFAP, DAG, α-SMA, Smad3, ß-amyloid and phospho-tau protein levels compared to controls. Carvedilol, propranolol, and doxazosin reversed all dexamethasone-induced molecular changes and slightly ameliorated the histopathological changes. Carvedilol significantly increased brain weight and ß-arrestin2 levels compared to dexamethasone, propranolol, and doxazosin groups. CONCLUSION: blocking α- and/or ß-adrenergic receptors alleviate dexamethasone-induced neurotoxicity despite their distinct effects on ß-arrestin2 levels in the cerebral cortex.

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Mirtazapine (MTZ) is an antidepressant drug with an exceptional pharmacological profile. It also has an excellent safety and tolerability profile. The present review provides a pharmacological update on MTZ and summarizes the research findings of MTZ's effects on different diseases. MTZ is hypothesized to have antidepressant effects because of the synergy between noradrenergic and serotonergic actions and is effective in treating major depressive disorder and depression associated with epilepsy, Alzheimer's disease, stroke, cardiovascular disease, and respiratory disease. In cancer patients, MTZ significantly reduced sadness, nausea, sleep disruption, and pain and improved quality of life. Also, it has promising effects on Parkinson's disease, schizophrenia, dysthymia, social anxiety disorder, alcohol dependency, posttraumatic stress disorder, panic disorder, pain syndromes, obsessive-compulsive disorder, and sleep disorders. Additionally, MTZ is potentially therapeutic in different situations associated with depression, such as liver, kidney, cardiovascular, respiratory, infertility, heavy metal-induced neurotoxicity, and pruritus. Potent antioxidative, anti-inflammatory, and anti-apoptotic bioactivities mediate these promising effects. These positive outcomes of the scientific investigations motivate more and more clinical trials for a golden exceptional antidepressant in different conditions.

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Chronic kidney disease (CKD) is one of the most prevalent chronic diseases and affects between 10 and 14 % of the world's population. The World Health Organization estimates that by 2040, the disease will be fifth in prevalence. End-stage CKD is characterized by renal fibrosis, which can eventually lead to kidney failure and death. Renal fibrosis develops due to multiple injuries and involves oxidative stress and inflammation. In the human body, nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in the expression of antioxidant, anti-inflammatory, and cytoprotective genes, which prevents oxidative stress and inflammation damage. Heme oxygenase (HO-1) is an inducible homolog influenced by heme products and after exposure to cellular stress inducers such as oxidants, inflammatory chemokines/cytokines, and tissue damage as an outcome or downstream of Nrf2 activation. HO-1 is known for its antioxidative properties, which play an important role in regulating oxidative stress. In renal diseases-induced tissue fibrosis and xenobiotics-induced renal fibrosis, Nrf2/HO-1 has been targeted with promising results. This review summarizes these studies and highlights the interesting bioactive compounds that may assist in attenuating renal fibrosis mediated by HO-1 activation. In conclusion, Nrf2/HO-1 signal activation could have a renoprotective effect strategy against CKD caused by oxidative stress, inflammation, and consequent renal fibrosis.

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Β-arrestins are intracellular scaffolding proteins that have multifaceted roles in different types of disorders. In this review article, we gave a summary about the discovery, characterization and classification of these proteins and their intracellular functions. Moreover, this review article focused on the hepatic expression of ß-arrestins and their hepatocellular distribution and function in each liver cell type. Also, we showed that ß-arrestins are key regulators of distinct types of hepatic disorders. On the other hand, we addressed some important points that have never been studied before regarding the role of ß-arrestins in certain types of hepatic disorders which needs more research efforts to cover.

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BACKGROUND AND OBJECTIVE: The most important presentation of COVID-19 is hyper inflammatory condition and cytokine storm that occurs due to excessive increase of the inflammatory mediators specially, pro-inflammatory interleukins such as IL-1ß, IL-6 and tumor necrosis factor-α which have an important role in the cytokine storm pathway. Up till now there is not a definitive treatment for COVID-19 disease, but according to the pathophysiology of the disease, Anakinra (Interleukin- 1 inhibitor) is an adjuvant treatment option in patients with severe COVID-19 by blocking the effect of IL-1. So, we aimed to summarize the studies that evaluated the safety and efficacy of Anakinra in patients diagnosed with COVID-19. METHODS: We performed a search in PubMed, Cochrane Library, Scopus, and Web of Science (WOS) databases from inception till 7 Jan 2022. Additionally, we searched randomized and non-randomized clinical trials, cohort, case series, case control, case report more than 3 patients which contain confirmed cases of COVID-19 who received Anakinra (Interleukin- 1 inhibitor) for the management of hyper-inflammatory condition associated with COVID-19 disease. A meta-analysis was conducted using review manager 5.4. RESULTS: We included 44 articles in the systematic review. Ultimately, 23 studies were incorporated in the meta-analysis with a total number of 3179 patients. Our analysis showed statistically significant difference in the following outcomes: duration of ICU stays [MD = -0.65, 95% CI (-1.09, -0.03), p = 0.04], the number of patients who needed invasive mechanical ventilation [RR = 0.57, 95% CI (0.39, 0.84), p = 0.004], and number of deaths [RR = 0.80, 95% CI (0.66, 0.99), p = 0.04]. Our analysis showed no statistically significant difference in the following outcomes: length of hospital stays [MD = -0.16, 95% CI (-0.42, 0.11), p = 0.26], oxygen-free days [MD = -0.81, 95% CI (-3.81, 2.20), p = 0.60], and the number of patients who needed non-invasive mechanical ventilation [RR = 1.09, 95% CI (0.47, 2.52), p = 0.84]. CONCLUSION: Anakinra showed some promising results in important outcomes related to COVID-19 as it significantly reduced the rate of mortality and the need of invasive mechanical ventilation. It should be used in severe cases more than mild and moderate cases to avoid possible immunosuppression complications. Anakinra use is safe in cases of COVID-19 at dose less than 100 mg. Another important outcome was significant reduction is the D-dimer level. Anakinra may be effective in the treatment of specific immunocompromised cases, but it should be used cautiously.

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