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Current understanding of metal ions in the pathogenesis of Alzheimer’s disease
Background
The homeostasis of metal ions, such as iron, copper, zinc and calcium, in the brain is crucial for maintaining normal physiological functions. Studies have shown that imbalance of these metal ions in the brain is closely related to the onset and progression of Alzheimer’s disease (AD), the most common neurodegenerative disorder in the elderly.
Main body
Erroneous deposition/distribution of the metal ions in different brain regions induces oxidative stress. The metal ions imbalance and oxidative stress together or independently promote amyloid-β (Aβ) overproduction by activating β- or γ-secretases and inhibiting α-secretase, it also causes tau hyperphosphorylation by activating protein kinases, such as glycogen synthase kinase-3β (GSK-3β), cyclin-dependent protein kinase-5 (CDK5), mitogen-activated protein kinases (MAPKs), etc., and inhibiting protein phosphatase 2A (PP2A). The metal ions imbalances can also directly or indirectly disrupt organelles, causing endoplasmic reticulum (ER) stress; mitochondrial and autophagic dysfunctions, which can cause or aggravate Aβ and tau aggregation/accumulation, and impair synaptic functions. Even worse, the metal ions imbalance-induced alterations can reversely exacerbate metal ions misdistribution and deposition. The vicious cycles between metal ions imbalances and Aβ/tau abnormalities will eventually lead to a chronic neurodegeneration and cognitive deficits, such as seen in AD patients.
Conclusion
The metal ions imbalance induces Aβ and tau pathologies by directly or indirectly affecting multiple cellular/subcellular pathways, and the disrupted homeostasis can reversely aggravate the abnormalities of metal ions transportation/deposition. Therefore, adjusting metal balance by supplementing or chelating the metal ions may be potential in ameliorating AD pathologies, which provides new research directions for AD treatment.
Journal Article
أفكار حول تعميق الإصلاح
يناقش الكتاب سلسلة من الإيضاحات الهامة قدمها الرئيس الصيني والأمين العام للجنة المركزية للحزب الشيوعي الصيني، شي جين بينغ، وتدور حول أفكار الإصلاح وتوسيع الانفتاح على نحو شامل في الصين. يضم الكتاب أكثر من 70 وثيقة هامة على صورة كلمات شي جين بينغ وخطاباته وتعليقاته وتوجيهاته وينقسم الكتاب إلى 12 موضوعا خاصا تتضمن 274 قطعة من مقتطفات الأقوال، نشر بعضها لأول مرة.
Book
The causal relationship between allergic diseases and heart failure: Evidence from Mendelian randomization study
Emerging evidence shows allergic diseases, such as atopic dermatitis and asthma, are risk factors of heart failure. However, the causal relationship between allergic diseases and heart failure is not clear. We performed a two-sample Mendelian randomization analysis between allergic diseases and heart failure using summary statistics of genome-wide association studies from large GWAS consortia, with total sample size of 1.2 million. Independent instrumental variables for asthma and atopic dermatitis (P<1x10.sup.-5) were used as the exposure. We applied five models for the Mendelian randomization analysis. Finally, we performed the sensitivity analyses to assess the robustness of the results. We have identified 55 independent single nucleotide polymorphisms (SNPs) for asthma 54 independent SNPs for atopic dermatitis as our instrumental variables. The inverse variance-weighted (IVW) analysis showed asthma was significantly associated with increased risk of heart failure (OR.sub.IVW = 1.04, 95% CI, 1.01-1.07, P = 0.03). The Mendelian randomization analysis using the other four models also showed consistent results with the IVW analysis. Similarly, atopic dermatitis was also significantly associated with an increased risk of heart failure (OR.sub.IVW = 1.03, 95% CI, 1.01-1.06, P = 0.01), consistent with the other four models. The sensitivity analysis showed no evidence of horizontal pleiotropy or results were driven by single SNPs. Our study identified asthma and atopic dermatitis as a causal risk factor for heart failure and suggest inflammatory pathogenesis as a key factor contributing to the underlying mechanism. These findings emphasize the importance of asthma and allergy control in the prevention and management of heart failure.
Journal Article
Pursuit : the Balvenie stories collection
\"What is it to pursue a goal, to strive for an ideal, to follow a dream? These are the questions explored by The Balvenie in this unique collection compiled by award-winning novelist Alex Preston. The stories - from some of the brightest and most exciting voices writing today - tell of determination, endeavour and perseverance against the odds. They range across wildly different contexts and cultures, from the epic to the intimate, in fiction and non-fiction, illustrating and illuminating the outer limits of human character and achievement.\"--Publisher description.
BOOK
Diagnostic and prognostic values of contrast-enhanced ultrasound in breast cancer: a retrospective study
This study aimed to explore the diagnostic and prognostic values of contrast-enhanced ultrasound (CEUS) in breast cancer. Between September 2009 and October 2011, a total of 143 breast cancer patients and 161 healthy people were selected as case group and control group, respectively. After the identification of lesions by conventional ultrasound, all patients underwent CEUS. The CEUS images were analyzed, and time-intensity curves (TICs) were obtained. Hematoxylin-eosin and immunohistochemistry staining was performed on tissue specimens, according to which the expressions of estrogen receptor (ER), c-erb-B2, p53, and Ki-67 were measured. Multivariate logistic regression analysis was used to compare CEUS and TIC parameters between the two groups. Compared with the control group, cancer patients showed high enhancement, heterogeneous enhancement or defects in the central region, expansion of lesion diameter after enhancement and crab-like blur lesion edges. The peak intensity (PI), relative start time of enhancement, relative PI, and relative area under the curve in the case group were significantly higher than those in the control group. Logistic analysis showed that the uniformity of enhancement, expansion of lesion diameter, and relative PI were significant diagnostic parameters of breast cancer, with area under the curve being 0.798, 0.776, and 0.919, respectively. There were strong associations between CEUS characteristics and expressions of prognostic factors in breast cancer: the heterogeneous enhancement was common in c-erb-B2-positive tumors; the centripetal enhancement occurred more in ER-negative tumors; perforator vessels were often seen in tumors at high histological grade; perfusion defects were common in ER-negative, c-erb-B2-positive, and Ki-67-positive tumors. CEUS is a useful tool for the early diagnosis and prognosis of breast cancer.
Journal Article
Controllable all-fiber generation/conversion of circularly polarized orbital angular momentum beams using long period fiber gratings
Mode-division multiplexing (MDM) is a promising technology for increasing the data-carrying capacity of a single few-mode optical fiber. The flexible mode manipulation would be highly desired in a robust MDM network. Recently, orbital angular momentum (OAM) modes have received wide attention as a new spatial mode basis. In this paper, we firstly proposed a long period fiber grating (LPFG) system to realize mode conversions between the higher order LP core modes in four-mode fiber. Based on the proposed system, we, for the first time, demonstrate the controllable all-fiber generation and conversion of the higher order LP core modes to the first and second order circularly polarized OAM beams with all the combinations of spin and OAM. Therefore, the proposed LPFG system can be potentially used as a controllable higher order OAM beam switch and a physical layer of the translating protocol from the conventional LP modes communication to the OAM modes communication in the future mode carrier telecommunication system and light calculation protocols.
Journal Article
Application of iontophoresis in ophthalmic practice: an innovative strategy to deliver drugs into the eye
Delivery of drugs to special locations of ocular lesions, while minimizing systemic and local toxic effects, is recognized as a critical challenge in the ophthalmic practice. The special anatomy and physiology barriers within the eyeball entail effective drug delivery systems. Emerging attempts in drug delivery has led to developments in ocular iontophoresis, which acts as a noninvasive technology to enhance drug penetration using a small electric current. This technique offers greater flexibility to deliver desired drug dose in a controlled and tolerable manner. In previous studies, this technique has been testified to deliver antibiotics, corticoid, proteins and other gene drugs into the eye with the potency of treating or alleviating diverse ophthalmological diseases including uveitis, cataract, retinoblastoma, herpes simplex and cytomegalovirus retinitis (CMVR), etc. In this review, we will introduce the recent developments in iontophoresis device. We also summarize the latest progress in coulomb controlled iontophoresis (CCI), hydrogel ionic circuit (HIC) and EyeGate II delivery system (EGDS), as well as overview the potential toxicity of iontophoresis. We will discuss these factors that affect the efficacy of iontophoresis experiments, and focus on the latest progress in its clinical application in the treatment of eye diseases.
Journal Article
Modified osteotomy for treatment of forearm deformities (Masada IIb) in hereditary multiple osteochondromas: a retrospective review
Purpose
Approximately 30% of patients with hereditary multiple osteochondromas (HMO) have forearm deformity and dysfunction. The aim of this retrospective study was to review our experience with the surgical treatment of children with HMO and Masada IIb forearm deformities.
Methods
Data of eight children treated for HMO Masada IIb forearm deformity at our hospital between 2015 and 2019 were collected from the hospital records and retrospectively reviewed. All patients underwent ulnar lengthening by distraction osteogenesis using either the Orthofix or Ilizarov external fixator. Range of movements at the elbow and wrist joints, and forearm supination/pronation, before and after the operation were recorded. Radiographs were evaluated by the Fogel method, and wrist joint function by the Krimmer method.
Results
Follow-up radiographs showed significant improvement in relative ulnar shortening after treatment (pre-operative 9.23 ± 5.21 mm; post-operative 0.33 ± 4.13 mm). Changes in radial articular angle (pre-operative 33.55° ± 3.88° to 32.78° ± 6.57°) and carpal slip (pre-operative 45.00% ± 19.09%; post-operative 43.13% ± 16.68%) were not significant. Elbow flexion and extension, wrist flexion and extension, ulnar and radial deviation at wrist, and forearm rotation were significantly improved after surgery. Wrist function was graded as excellent in seven patients and as good in one patient. One patient treated with the Ilizarov external fixator had poor radial head reduction.
Conclusion
Ulnar lengthening with distraction osteogenesis is an effective treatment for HMO Masada IIb deformities. The optimum site for ulnar osteotomy appears to be at the proximal one-third to one-fourth of the ulna.
Journal Article
Genetic mechanisms of arsenic detoxification and metabolism in bacteria
Arsenic, distributed pervasively in the natural environment, is an extremely toxic substance which can severely impair the normal functions of living cells. Research on the genetic mechanisms of arsenic metabolism is of great importance for remediating arsenic-contaminated environments. Many organisms, including bacteria, have developed various strategies to tolerate arsenic, by either detoxifying this harmful element or utilizing it for energy generation. This review summarizes arsenic detoxification as well as arsenic respiratory metabolic pathways in bacteria and discusses novel arsenic resistance pathways in various bacterial strains. This knowledge provides insights into the mechanisms of arsenic biotransformation in bacteria. Multiple detoxification strategies among bacteria imply possible functional relationships among different arsenic detoxification/metabolism pathways. In addition, this review sheds light on the bioremediation of arsenic-contaminated environments and prevention of antibiotic resistance.
Journal Article