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L-Carnitine (Lc) acts as an antioxidant that neutralizes free radicals, especially superoxide anions and protects cells against oxidative damage-induced apoptosis, as following ovulation, intracellular reactive oxygen species (ROS) accumulation increases in oocytes, Oocytes exhibit an intracellular defense mechanism against an oxidative attack. This outcome adversely affects fertilization and subsequent embryonic development, thereby increasing the risk of an early miscarriage and abnormal development of offspring. The purpose of this study was to see how adding LC to either maturation or fertilization medium affected the developmental competence of immature bovine oocytes. In this study, Ovaries from apparently normal reproductive organs of cattle were collected within 30 minutes from slaughter and evisceration of animals. Cumulus oocyte complexes (COCs) were collected by aspiration of medium sized ovarian follicles (4-8 mm). COCs of acceptable quality were selected, washed and incubated in tissue culture media 199 (TCM199) supplemented with 10% heat inactivated fetal calf serum, 5 μg/ml luteinizing hormone (LH), 0.5 μg/ml follicle stimulating hormone (FSH) and 1 μg/ml estradiol-17β for 20:22 hour at 38.5 C◦ under 5% CO2 in air with 90% humidity. different concentrations of LC (1.25,2.5 and 5mM) were used. The results were consistent for both maturation and fertilization and there is a significant increase in maturation, fertilization., cleavage and blastocyst rate. In conclusion, LC has important role in IVEP through addition of LC to maturation media or culture media it improved nuclear maturation and blastocyst formation rates in bovine oocytes.
Commotio retinae (CR) is a condition frequently observed in clinical practice, particularly following closed globe trauma (CGT) due to sport, labor, or traffic accident injuries. It is the main cause of unilateral vision loss in male patients aged between. It is characterized by transient gray-white retinal coloration and reduction of visual acuity (VA). Symptoms depend mainly on the location and severity (deep) of the injury, with less complains when only the superficial or peripheral retina is affected. It may be confined to the posterior pole, when it is also called Berlin’s edema, after the first hypothesis of Berlin (1873). There is no specific treatment since the treatment depends on the region of the retina and choroid affected. In this work we report a case of Berlin edema, treated with ǪIAPI 1®, to restore the balance of oxygen, which is generated at the intracellular level.
Introduction Calcium (Ca2+) plays an important role in the pathogenesis of ischemic cell damage. Intracellular Ca2+ accumulation leads to neuronal damage by triggering the cycle of cytotoxic events, however the relationship of serum Ca levels and the pathways involved in ischemic injury is unclear. Aim of Study To investigate the relationship of serum Ca2+ levels with severity of acute ischaemic stroke, serum calcium (Ca2+) levels were measured within the first 48 hours and were compared with the clinical severity of acute ischaemic stroke. Material and Methods A hospital based cross sectional study was performed among 100 patients of acute ischaemic stroke who fulfilled the inclusion criteria. The Study was done from July 2020 to August 2021 in SPRC & Neurology Hospital Dhaka, Bangladesh And BSMMU Hospital Dhaka, Bangladesh. After hospitalization presenting complaints, physical findings of the patients were recorded. Severity of stroke was measured by NIHSS scale. Serum calcium level of every patient was measured. Calcium level was divided into 3 groups by weighted average. Statistical analysis was carried out by a non-parametric Ruska Wallis test. Results Among the 100 patients 59% were male. Among all patients 57% of patients were found to be smokers (98% male, 2% female). Among all patients 63% patients were found hypertensive and 21% of all patients (24% male, 17% female) were diabetic. Mean cholesterol level was 257.98mg/dl with standard deviation 55.49 which is above the reference range suggesting hypercholesterolemia, Triglyceride was borderline and LDL cholesterol was slightly higher and HDL cholesterol was slightly lower. Calcium level was divided into 3 groups and NIHSS score was calculated for every patient in each group. The median NIHSS score for group1 (calcium level ≤8.8 mg/dl) was 9(2-20), for group 2 (calcium level 8.9-9.6 mg/dl) was 6 (1-17) and for group 3 (calcium level ≥9.7mg/dl) was 4 (1-16). Conclusion Commonest risk factor of ischaemic stroke is hypertension. Other risk factors are smoking, diabetes mellitus and hyperlipidemia, cardiac disease. Higher serum calcium level is associated with less severity of ischaemic stroke.
Background Local anesthetic neurotoxicity is a common complication in clinical anesthesia, which can cause permanent nerve damage in severe cases. The T-type calcium channel is an important channel for regulating the excitability of neurons. Normally, extracellular calcium ions enter the cell through the T-type calcium channel to change the excitability of neurons. When the intracellular calcium is overloaded, it can cause cell damage. Aims To investigated the roles of T-type calcium channel in the SH-SY5Y cells injury induced by the bupivacaine. Methods The SH-SY5Y cell culture model was used to observe the effect of T-type calcium channel blocker NNC55-0396 on the neurotoxicity of bupivacaine hydrochloride by MTT methold,flow cytometry, Western blotting and other methods. Results The results show that NNC55-0396 can block the T-type calcium channel of SH-SY5Y cells, improve the decrease of cell viability caused by bupivacaine hydrochloride, reduce the level of intracellular calcium ion, reduce the expression of Cleavedcaspase-3, and reduce cell apoptosis. Conclusion The above results indicate that the T-type calcium channel is involved in the SH-SY5Y cell damage caused by bupivacaine hydrochloride, and blocking the T-type calcium channel can reduce the neurotoxicity of bupivacaine hydrochloride.
Conversion of biomass into fermentable sugars is a major requirement for successful and cost-effective biofuels production. The conversion of xylan to sugars requires multiple enzymes including α-glucuronidase. Here we report the cloning, expression, purification and characterization of the α-glucuronidase from Dictyoglomusturgidum(DtuAgu). DtuAgu is an intracellular protein of 685 amino acids and a predicted molecular weight of 79.4 kD. Enzymatic activity was optimum between pH 7.0 and 8.0 and at 85°C. The specific activity of the enzyme was 10 u/mg when measured using mixed aldouronic acids. The specific activity on isolated glucuronoxylan was approximately 20% of the value obtained with xylooligosaccharides. DtuAgu significantly improved xylan conversion to xylose when evaluated using two mixtures of thermostable bacterial enzymes and two sources of xylan. DtuAgu has the potential to be a key player in thermostable enzyme cocktails for the conversion to biomass to biofuels.α
The effect of resveratrol, a free radical scavenger, during cataract development was evaluated in the Wistar rat pup model. This study investigated the possible free radical scavenging potential of resveratrol at 40 mg/ kg body wt dose in selenite-induced cataract in rat pups. Intraperitoneal injection of sodium selenite (15 µm mol/ kg body wt) in 8 to 10 day old rat pups lead to severe oxidative stress in the tissues evidenced by decreased antioxidants and increased lipid peroxidase, nitric oxide, superoxide anion, hydroxyl radical generation, inducible nitric oxide synthase (iNOS) as well as nuclear factor kappa B (NF-kB) expression levels that probably led to cataract formation. Selenite exposure also caused an increase in total calcium in the eye lens and significantly inhibited the activity of Ca2+ ATPase but not Na+/ K+ ATPase or Mg2+ ATPase. However, both pre- and co-treatments with resveratrol, but not post-treatment, led to an increase in antioxidant levels with a concomitant reduction in oxidative stress and also rescued the selenite-mediated increase in lens Ca2+ and inhibition of Ca2+ ATPase activity in the eye lens. The results of this study demonstrate antioxidants decrease and increase in free radical generation triggered by selenite causes the inactivation of lens Ca2+ ATPase leading to a rise in intracellular Ca2+ level. Resveratol treatment was able to prevent selenite-induced oxidative stress and in turn the inhibition of lens opacification. Thus, resveratrol has the potential to function as an anti-cataractogenic agent, possibly by preventing free radical-mediated accumulation of Ca2+ in the eye lens.
Aging mammalian skeletal muscle satellite cells (MuSCs) undergo a decline of stem cell/progenitor cell proliferative and regenerative capacity, and the development of a physiological milieu characteristic of a state of chronic sterile inflammation. p38αMAPK and ERK1/2 are two major signaling pathways that regulate the age-associated decline of MuSC proliferative capacity. In this review we propose the following mechanism that links the p38αMAPK pathway to the decline of self-renewal and regenerative capacity of aged MuSCs: a) the HS-FGF-2-FGFR1-p38αMAPK-Axis, a tightly linked homeostatic signaling complex, is in synchrony with the autoinhibition of FGFR1; b) autoinhibition contributes to the Axis’ regulation of the homeostasis of P-p38αMAPK activity in juvenile MuSC; c) this combination of protein-protein interactions is characteristic of a juvenile cytoplasmic milieu of beneficial P-p38αMAPK activity and d) includes Sprouty1 inhibition that supports the stimulation of FGF-2 --> miR-29a; e) the miR29a dismantles the basement membrane in preparation for the initiation of replication; f) an age-associated impaired, dysregulated, over-sulfated heparan sulfate ligand (HS)-FGF-2 fails to activate FGFR1 in aged MuSCs; g) this uncouples its regulation of p38αMAPK and ERK1/2 pathways and results in desensitization of FGFR1; h) desensitization of FGFR1 and Sprouty1 interaction in aged MuSC uncouples their regulation of P-p38αMAPK in the aged MuSCs; i) this enables a state of chronic sterile inflammation to promote and sustain an increased level of P-p38αMAPK activity; and, j) the increased activity of P-p38αMAPK in aged MuSC stimulates the production of cell cycle inhibitors, miR-1 and miR-133, thereby attenuating the expression of the cell cycle regulators, SP1 and cyclin D1, resulting in a G1/S arrest; j) the increased level of p38αMAPK activity promotes the apoptosis of the aged activated MuSCs. This mechanism involves the synergistic interactions of HS-FGF2-FGFR-1, Sprouty (spry1), miR-1, miR-133 and miR-29a that unify the extracellular niche and intracellular milieu for the juvenile vs age-associated regulation of proliferative capacity of the MuSC. Our hypothesis unifies these interactions with the role of the extracellular niche and intracellular milieu in the stimulation of juvenile proliferation vs age-associated decline of skeletal muscle satellite cell self-renewal and regenerative proliferation. Word Count = 344
This letter presents a clinician's perspective on the biological basis of diabetes mellitus at the cellular level. Drawing on neurosurgical practice, the author argues that persistent dysglycemia hinders recovery and may reflect long-standing intracellular processes, calling for causal, interdisciplinary management beyond symptomatic care. The piece outlines testable hypotheses and invites further laboratory validation.
Journal of Biosemiotic Research is a new periodical devoted to a young, actively developing science. A review of recent scientific publications shows that in the broad scientific space of biosemiotics contemporary questions and "eternal themes" interact, not finding an answer in the private sciences - anthropology, semiotics of culture and philosophy1,2. To solve them, the fundamental foundations of science and new achievements, the opportunities of the latest technologies and scientific communications are attracted. Like all young sciences, biosemiotics has many definitions. We give here the most famous ones. "Biosemiotics: (bios, life + semion = sign) is an interdisciplinary field of theoretical and empirical research, analyzing communication and signification in living systems. Signed processes, ranging from molecular to ecological and evolutionary, have been studied throughout the history of biology; however, very often descriptions of information and communication aspects of living systems were considered only metaphorical, believing that the essence of them can be understood with the help of physical and chemical descriptions. In biosemiotics, on the other hand, information sign processes are considered as the primordial, basic system of phenomena of life, requiring a new understanding..."3. "Biosemiotics explores sign systems of various levels: molecular biological (genetic code), intracellular (signal peptides), intercellular (mediators, immune interactions), intraorganism (hormones, conditioned reflex reactions) and interorganism (telergons, pheromones, attractants) ... In addition, biosemiotics covers all the problems associated with the problem of the existence of language and thinking in animals." However, today we can go further and add to the analysis the next stage of evolution, standing between animals and modern human (Homo sapiens sapiens).
Breast cancer (BC) is the leading cause of cancer-related deaths in young to middle-aged women worldwide. Moreover, the survival rate in BC-patients is only 20% when associated with metastatic disease. The high mortality rate observed in BC women with metastatic disease has precipitated a major challenge revealing an unmet need to develop new therapeutic strategies in treating metastatic cancer. One such approach has involved utilization of chemokines and their receptors as therapeutic targets for cancer metastasis. It has been established that a definitive correlation exists between overexpressed CXCR4 malignant cell receptors and cancer cell growth, invasion, and migration. It is also widely accepted that the CXCR4 receptor, complexed to its CXCL12 ligand, plays a major role in establishing migratory pathway gradients for cancer cells migrating to distant tissues/organ sites. It would follow that chemokine decoy ligands, such as peptide antagonists and inhibitors, could serve to induce receptor blockade and impede subsequent intracellular signaling. Such ligands, synthetic and natural, reportedly contribute to reducing cancer cell growth, invasion, adherence, and migration. The present commentary describes several existing synthetic CXCR4 receptor-ligand peptide antagonists and presents a strategy to develop naturally-occurring human protein-derived peptide candidates.
All independent experimental data on epithelial and glandular cells lines of human endometrium support the evidence for a rapid production of eicosanoids from the LH/hCG receptors when exposed to the hCG hormone. Prostaglandins rapidly act on the surrounding endometrial stromal cells throughout the adenylyl cyclase enzyme leading to very large amounts of cAMP and angiogenic factors (VEGF) production. The cAMP is the most important intracellular second messenger and along with progesterone accomplishes the full process of decidualization and acquisition of receptivity after estrogenic priming of the endometrium. The status of uterine receptivity lasts few days only and timing for successful embryo-signal transduction system activation by the endometrium is probably short. In absence of in vivo embryonic signals it is impossible to predict, on individual bases, how the intensity of all the complex interlinked molecular changes of decidualization might ever be in case of exposure to native hCG. In other terms, amount of prostaglandins and cAMP produced in response to variably glycosylated hCG are all, in vivo, not measurable variables and should be viewed as a “wave” of biochemical chain reactions. Embryonic hCG is secreted in form of multiple isomers having an unpredictable variable level of glycosylation and control of this variable remains elusive. During cycles of ovarian stimulation many drugs (FSH, LH, HCG) interact with different G-protein coupled receptors (GPCRs) making it possible to alter the prostaglandins-mediated decidualization process ready to be elicited only by hCG of pregnancy. Since the molecules (cAMP and progesterone) controlling endometrial stromal cells differentiation into decidual cells are critical for successful implantation and placenta formation, the evidence of fast eicosanoids production associated with endometrial LH/hCG receptors exposure to hCG and the potential by human endometrium to produce, in response, very large amounts of cAMP has biological and clinical relevance.
Malaria is a mosquito-transmitted infectious disease caused by intracellular protozoan parasites of the genus Plasmodium. In the absence of prompt and appropriate treatment contraction of primary infection by a human being often represents a medical emergency since it may progress rapidly to life-threatening complications. Exposure to parasites activates the immune system resulting in, among other effects, the release of reactive oxygen intermediates (ROI). This has the potential to induce oxidative damage, thereby causing cellular destruction, and hence to have a severe effect on vital organs of the body. Overexpression of ROI leads to immunosuppression and is a causal factor in the development of malaria-related disease symptoms. However, the body possesses various defence mechanisms, notably including the production of antioxidants, which are capable of reducing the cellular effects of ROI. Antioxidants are either sourced exogenously from the diet or synthesized through different intracellular mechanisms. Antioxidants that include glutathione peroxidase, catalase, EDTA and vitamin C suppress the initial production of ROI. Others such as uric acid, superoxide dismutase and vitamin E may also inhibit potentially damaging products of ROI metabolism. Current anti-malarial drugs often have damaging side-effects, as exemplified by memory impairment following treatment for cerebral malaria. Recent studies have explored the potential use of antioxidants alone or in combination with anti-malarials as a therapeutic means to negate Plasmodium-induced oxidative stress and its associated metabolic complications. It is indicated that when utilized in an adjuvant capacity antioxidants of natural and synthetic origin may improve anti-malarial therapy by causing less damage to the host during malaria infection.
Perkinsus marinus is an intracellular parasitic protozoan that is responsible for serious disease epizootics in marine bivalve mollusks worldwide. Despite all available information on P. marinus genomics, more baseline data is required at the proteomic level. Our aim was to study the proteome profile of in vitro cultured P. marinus isolated from oysters Crassostrea spp. using a label-free shotgun UDMSE approach. A total of 4073 non-redundant proteins were identified across three biological replicates with stringent identification. Proteins specifically related to adaptive survival, cell recognition, antioxidants, regulation of apoptosis and others were detected. Important virulence factors of P. marinus were identified including serine protease and iron-dependent superoxide dismutase. Other proteins with involvement in several pathogens invasion strategies were rhoptries, serine-threonine kinases, and protein phosphatases. Interestingly, peptides corresponding to retroviruses polyproteins were identified in all replicates. The interactomic analysis of P. marinus proteins demonstrated extensive clusters network related to biological processes. In conclusion, we provide the first comprehensive proteomic profile of P. marinus that can be useful for further investigations on Perkinsus biology and virulence mechanisms.
General anesthetics (GAs) are widely used for various essential surgical or medical procedures. Recent studies implicate the GAs has dual effects of neuroprotection and neurotoxicity on neurogenesis with unclear mechanisms. This minireview summarizes recent studies on GAs mediated effects on neurogenesis and proposed mechanisms, with focus on autophagy regulation and intracellular calcium homeostasis.
Telomeres are strings of DNA that are not themselves genes but that extend every chromosome beyond its last gene. Terminal telomeres are sacrificed during every mitotic event in human cells (“telomere attrition”), preserving the functional genome despite the “end replication problem.” However, the “telomeric theory of biological aging” suggests that when an individual cell has reproduced itself a sufficient number of times (the “Hayflick limit”), some the its telomeres have become critically shortened (“telomeric crisis”) and cannot completely “cap off” a chromosome, and any further attempts to replicate such a chromosome would produce damaged DNA and a dysfunctional cell (“cellular aging”). As cells enter telomeric crisis, they usually initiate intracellular signaling cascades that arrest DNA replication and mitotic activity, converting biologically active cells into inactive cells (“cellular senescence”). The progressive accumulation of senescent cells impairs the healthy functioning of tissues and produces “biological aging.” Oxidative stress damages telomeres and accelerates telomere attrition and biological aging. Premature biological aging is associated with degenerative diseases and diminished quality of life. Reducing the level of systemic oxidative stress can ease the oxidative drive toward cellular senescence and premature biological aging. Increased intakes of antioxidant-rich foods and specific antioxidant nutrients (such as fruits and vegetables, α -lipoic acid, astaxanthin, eicosapentaenoic acid, docosahexaenoic acid, trans-resveratrol, N-acetylcysteine, methylsulfonylmethane, lutein, vitamin C, vitamin D, vitamin E, and γ-tocotrienol) may decrease cellular and systemic oxidative stress and decelerate biological aging.
Gold nanorods (GNRs) are plasmonic nanostructures by virtue of their size-dependent optical properties, offer a bionanotechnology platform in areas of bioimaging, drug delivery etc for disease diagnosis, prognosis, and therapy. GNRs are more sensitive to changes in local environments, and offer strong scattering and absorption efficiencies thus providing opportunities to integrate multiple imaging modes and therapeutic strategies. The hydrodynamic size of these GNR under physiological condition is <100 nm, making them ideal as intracellular delivery agents. RNA interference using small inhibitory RNA (siRNA) has become a powerful tool to downregulate mRNA levels by cellular nucleases that become activated when a sequence homology between the siRNA and a respective mRNA molecule is detected. siRNA is used to silence genes involved in the pathogenesis of various diseases and holds a promising option for the development of novel therapeutic strategies in neurological dysregulation such as that observed in drug addiction. However, a major challenge in gene therapy continues to be effective delivery of siRNA and its sustained release at targeted sites. Previously, we have shown the GNR coated with poly (diallyldimethyl ammoniumchloride) (GNR-PDDAC) electrostatically complexed to the dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) siRNA forming a GNR-nanoplex that was able to effectively silence the DARPP-32 gene expression in dopaminergic neuronal (DAN) cell cultures in- vitro. The current report, explores if modification of the surface coating properties of the GNRs with different surface coatings namely, amino terminated polyethylene glycol (GNR-PEG), polyethyleneimine (GNR-PEI) and Chitosan (GNR-CIT) alters their stability, cytotoxicity and DARPP-32 gene silencing efficiency in-vitro dopaminergic neuronal (DAN) cell cultures with the goal of determining the most suitable surface coating for the GNR that would provide a GNR-nanoplex with the most stability, least cytotoxicity and most efficacious gene silencing.