Antiproliferative effect of Solanum nigrum L. water extract on breast can-cer cells: potential roles of apoptosis and oxidative stress.

Breast cancer is the most progressive cancer among women worldwide. The currently available chemotherapeutic agents induce severe unacceptable adverse effects in breast cancer patients. In this context, natural medicinal herbs are gaining importance to find non-toxic effective anticancer drugs. Solanum nigrum is one of the major traditional medicinal plants widely used in Ayurveda for the treatment of various diseases. This study investigated the anticancer effect of Solanum nigrum water extract (SNWE) against MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines. SNWE significantly induced oxidative stress-mediated apoptotic cell death in a concentration-dependent manner. Real-time PCR results illustrated the upregulation of proapoptotic genes and downregulation of antiapoptotic genes after SNWE treatment in MCF-7 and MDA-MB-231 cell lines. Immunofluorescence analysis showed increased expressions of apoptotic markers like p53, Caspase3 and BAX by SNWE treatment. In conclusion, the findings of this study indicate the antiproliferative effect and apoptosis-inducing property of SNWE in both cell lines. Further studies are warranted on testing the anticancer activity of S. nigrum L. using animal models of cancer.

The Role of Mitochondrial Dysfunction in Cytotoxic Effects of Solanum nigrum Water Extract on MCF-7 and MDA-MB-231 Breast Cancer Cells.

BACKGROUND: Recent studies suggest that numerous naturally occurring agents have the potential to kill cancer cells via mitochondrial dysfunction. Solanum nigrum is a herb widely used in alternative medical systems. This study aimed to investigate the cytotoxic effect of Solanum nigrum water extract (SNWE) against Michigan Cancer Foundation-7 (MCF-7) and MD Anderson-Metastatic Breast Cancer-231 (MDA-MB-231) cells. METHODS: We used an MTT reduction assay for cytotoxicity analysis. To explore the mode of action, the cellular adenosine triphosphate (ATP) levels and mitochondrial membrane potential were analyzed using a colorimetric ATP assay and Rhodamine-123 fluorescent staining, respectively, during SNWE treatment for 72 h. RESULTS: The cytotoxic effect was significant in both cell lines, with IC50 values of 4.26 µg/mL and 5.30 µg/mL in MCF-7 and MDA-MB-231 cells, respectively. The 24, 48, and 72 h treatments of 100 µg/mL SNWE showed 0.85 ± 0.07, 0.38 ± 0.1, and 0.20 ± 0.1 nM ATP in MCF-7 cells and 0.94 ± 0.07, 0.84 ± 0.2 and 0.46 ± 0.2 nM in MDA-MB-231 cells, respectively. The SNWE treatment altered the mitochondrial membrane potential (ΔΨm) in a concentration-dependent manner in both the breast cancer cell lines, to 29.6 ± 4.1% in MCF-7 and 28.7 ± 4.17% in MDA-MB-231 cells, when compared with healthy mitochondria (100% ΔΨm). CONCLUSIONS: The cytotoxic effects of Solanum nigrum against breast cancer cells are associated with energy metabolism. Additional studies are warranted to test the anticancer effect of Solanum nigrum using an animal model of breast cancer.

Complement Activation-Independent Attenuation of SARS-CoV-2 Infection by C1q and C4b-Binding Protein.

The complement system is a key component of the innate immune response to viruses and proinflammatory events. Exaggerated complement activation has been attributed to the induction of a cytokine storm in severe SARS-CoV-2 infection. However, there is also an argument for the protective role of complement proteins, given their local synthesis or activation at the site of viral infection. This study investigated the complement activation-independent role of C1q and C4b-binding protein (C4BP) against SARS-CoV-2 infection. The interactions of C1q, its recombinant globular heads, and C4BP with the SARS-CoV-2 spike and receptor binding domain (RBD) were examined using direct ELISA. In addition, RT-qPCR was used to evaluate the modulatory effect of these complement proteins on the SARS-CoV-2-mediated immune response. Cell binding and luciferase-based viral entry assays were utilised to assess the effects of C1q, its recombinant globular heads, and C4BP on SARS-CoV-2 cell entry. C1q and C4BP bound directly to SARS-CoV-2 pseudotype particles via the RBD domain of the spike protein. C1q via its globular heads and C4BP were found to reduce binding as well as viral transduction of SARS-CoV-2 spike protein expressing lentiviral pseudotypes into transfected A549 cells expressing human ACE2 and TMPRSS2. Furthermore, the treatment of the SARS-CoV-2 spike, envelope, nucleoprotein, and membrane protein expressing alphaviral pseudotypes with C1q, its recombinant globular heads, or C4BP triggered a reduction in mRNA levels of proinflammatory cytokines and chemokines such as IL-1ß, IL-8, IL-6, TNF-α, IFN-α, and RANTES (as well as NF-κB) in A549 cells expressing human ACE2 and TMPRSS2. In addition, C1q and C4BP treatment also reduced SARS-CoV-2 pseudotype infection-mediated NF-κB activation in A549 cells expressing human ACE2 and TMPRSS2. C1q and C4BP are synthesised primarily by hepatocytes; however, they are also produced by macrophages, and alveolar type II cells, respectively, locally at the pulmonary site. These findings support the notion that the locally produced C1q and C4BP can be protective against SARS-CoV-2 infection in a complement activation-independent manner, offering immune resistance by inhibiting virus binding to target host cells and attenuating the infection-associated inflammatory response.

Serum Levels of Proinflammatory Biomarkers in Military Recruits with and without Metabolic Syndrome.

Objectives: Inflammatory mediators are associated with many chronic diseases; however, their role in metabolic syndrome (Met-S) is not well documented. We therefore aimed to compare the serum markers of inflammation including C-reactive protein (CRP), myeloperoxidase (MPO), interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), and TNF-ß in young military recruits with and without Met-S. We hypothesized that any significant change in inflammatory markers between the two groups would indicate the role of inflammation in Met-S that would help in future directions for screening and treatment of Met-S. Design and Methods. A total of 2010 adult men, aged 18-30 years, were divided into two groups: with Met-S (N = 488) and without Met-S (N = 1522), according to the International Diabetes Federation definition. We compared the serum levels of inflammatory biomarkers between the two groups. We also studied the correlations between the inflammatory markers and the components of Met-S to explore the biomarker potential of inflammatory markers for screening of Met-S. Logistic regression analysis was performed to test the association between inflammatory markers and Met-S. Results: A large number of subjects in the Met-S group were suffering from obesity. Out of the 2010 total subjects, only 731 (36.4%) had normal fasting blood sugar (FBS), while the prevalence of prediabetes and diabetes was significantly higher in subjects with Met-S. We observed significant increases in serum levels of CRP, MPO, IL-6, and TNF-ß but not TNF-α in subjects with Met-S as compared to subjects without Met-S. All the markers of inflammation showed significant correlations with Met-S, triglycerides (TG), blood pressure, body mass index (BMI), and age; however, none of these markers were correlated with HDL. Logistic regression analysis showed a significant association between Met-S and inflammatory markers. Conclusions: Serum levels of CRP, MPO, IL-6, and TNF-ß are significantly increased in young adults with Met-S. This is probably the first study reporting TNF-ß levels in Met-S. Since a proinflammatory cascade precedes many years before the onset of cardiovascular disease, these inflammatory biomarkers could help in the monitoring of high-risk individuals with Met-S who will be requiring therapeutic intervention.

Assessment of ichthyofaunal diversity of family Cyprinidae in River Panjkora Dir, Khyber Pakhtunkhwa, Pakistan.

The study explores the Ichthyofaunal diversity of freshwater Cyprinidae fish in the Panjkora River of Dir, Khyber Pakhtunkhwa, Pakistan. A total of 911 fish samples were collected from 5 different sites along the river and identified using standard identification keys. Out of the 911 fish samples, 204 were related to family Cyprinidae, having 4 sub families, i.e Cyprininae representing 3 species i.e Carassius auratus, Cyprinus carpio, Cyprinus watsoni, Danioninae representing 6 species i.e Barilius modestus, Barilius vagra, Barilius pakistanicus, Amblypharangodon mola, Salmophasia punjabensis, Rasbora daniconius, Labeoninae representing 5 species i.e Tor putitora, Crossocheilus diplocheilus, Gara gotyla, Labeo rohita, Labeo diplocheilus, and Barbinae representing 6 species i.e Puntius ticto, Puntius sophore, Puntius chonchonius, Schizothorax esocinus, Schizothorax labiatus and Schizothorax plagiostomus. This study adds 6 new species i.e Amblypharangodon mola, Salmophasia punjabensis, Labeo rohita, Labeo diplocheilus, Puntius chonchonius and Rasbora daniconius for the 1st time which are not reported earlier. EXCEL 2019 and XLSTAT were used for principal components analysis to study richness and correlation of fish diversity. Eigenvalues obtained from Sheringal to Zulam are 3.72, 0.511, 0.37, 0.29 and 0.09 respectively. The higher eigenvalue of Sheringal site shows higher diversity. Water quality study shows that the mean values of water temperature was 16.8°C, pH 7.08, total hardness134.6 mg/L, alkalinity 89.3 mg/L, Nitrate 5.93 mg/L, Chlorine 0.87 mg/L, Nitrite0.02 mg/L and Copper 0.04 mg/L, Iron 0.07 mg/L, Lead 0.002 mg/L. The physicochemical parameters of river Panjkora during the study time remained within the permissible limits as prescribed by the WHO (2005). Gut analysis revealed the presence of algae, nymphs insect's larvae, macroinvertebrates and protozoans.

Laparoscopic sleeve gastrectomy for obesity treatment in adolescents and young adults: a systematic review and meta-analysis.

BACKGROUND: The incidence of obesity has been increasing in younger population, posing a significant impact on adolescents' life and health care system worldwide. METHODS: We critically analyzed the existing literature on the use of laparoscopic sleeve gastrectomy (LSG) for the treatment of obesity. We performed an in-depth evaluation of 37 studies and analyzed the effect of LSG in 2300 patients, aged ≤ 22 years. RESULTS: Mean body mass index (BMI) loss after LSG was 17.81 kg/m2. Gastroesophageal reflux was the most common complication. Most of the patients showed remission of comorbidities including hypertension, diabetes, and obstructive sleep apnea after LSG. CONCLUSIONS: These findings suggest that surgical intervention is highly beneficial for reducing BMI in appropriately selected adolescents and young adults suffering from obesity and comorbidities such as life-threatening obstructive sleep apnea.

Hybrid Nanoparticles of Manganese Oxide and Highly Reduced Graphene Oxide for Photodynamic Therapy.

BACKGROUND: Graphene-based nanomaterials possess unique optical, physicochemical and biomedical properties which make them potential tools for imaging and therapy. Manganese oxide nanoparticles are attractive candidates for contrast agents in magnetic resonance imagint (MRI). We used manganese oxide (Mn3O4) and highly reduced graphene oxide (HRG) to synthesize hybrid nanoparticles (HRG-Mn3O4) and tested their efficacy for photodynamic therapy (PDT) in breast cancer cells. METHODS: The newly synthesized nanoparticles were characterized by transmission electron microscopy (TEM), energy-dispersive X-ray (EDX) spectroscopy, UV-visible spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, thermogravimetry, and X-ray diffraction (XRD) analyses. We used standard protocols of cytotoxicity and PDT after exposing A549 cells to various concentrations of hybrid nanoparticles (HRG-Mn3O4). We also performed fluorescence microscopy for live/dead cellular analysis. A549 cells were incubated with nanoparticles for 24 h and stained with fluorescein diacetate (green emission for live cells) and propidium iodide (red emission for dead cells) to visualize live and dead cells, respectively. RESULTS: The cell viability analysis showed that more than 98% of A549 cells survived even after the exposure of a high concentration (100 µg/mL) of nanomaterials. These results confirmed that the HRG-Mn3O4 nanoparticles are nontoxic and biocompatible at physiological conditions. When the cell viability analysis was performed after laser irradiation, we observed significant and concentration-dependent cytotoxicity of HRG-Mn3O4 as compared to Mn3O4 nanoparticles. Fluorescence microscopy showed that almost 100% cells were viable when treated with phosphate buffered saline or Mn3O4 while only few dead cells were detected after exposure of HRG-Mn3O4 nanoparticles. However, laser irradiation resulted in massive cellular damage by HRG-Mn3O4 nanoparticles which was directly related to the generation of reactive oxygen species (ROS). CONCLUSIONS: HRG-Mn3O4 hybrid nanoparticles are stable, biocompatible, nontoxic, and possess therapeutic potential for photodynamic therapy of cancer. Further studies are warranted to explore the MRI imaging ability of these nanomaterials using animal models of cancer.

Three-Dimensional Graphene-TiO2-SnO2 Ternary Nanocomposites for High-Performance Asymmetric Supercapacitors.

Ternary nanocomposites synergistically combine the material characteristics of three materials, altering the desired charge storage properties such as electrical conductivity, redox states, and surface area. Therefore, to improve the energy synergistic of SnO2, TiO2, and three-dimensional graphene, herein, we report a facile hydrothermal technique to synthesize a ternary nanocomposite of three-dimensional graphene-tin oxide-titanium dioxide (3DG-SnO2-TiO2). The synthesized ternary nanocomposite was characterized using material characterization techniques such as XRD, Raman spectroscopy, FTIR spectroscopy, FESEM, and EDXS. The surface area and porosity of the material were studied using Brunauer-Emmett-Teller (BET) studies. XRD studies showed the crystalline nature of the characteristic peaks of the individual materials, and FESEM studies revealed the deposition of SnO2-TiO2 on 3DG. The BET results show that incorporating 3DG into the SnO2-TiO2 binary nanocomposite increased its surface area compared to the binary composite. A three-electrode system compared the electrochemical performances of both the binary and ternary composites as a battery-type supercapacitor electrode in different molar KOH (1, 3, and 6 M) electrolytes. It was determined that the ternary nanocomposite electrode in 6 M KOH delivered a maximum specific capacitance of 232.7 C g-1 at 1 A g-1. An asymmetric supercapacitor (ASC) was fabricated based on 3DG-SnO2-TiO2 as a positive electrode and commercial activated carbon as a negative electrode (3DG-SnO2-TiO2//AC). The ASC delivered a maximum energy density of 28.6 Wh kg-1 at a power density of 367.7 W kg-1. Furthermore, the device delivered a superior cycling stability of ∼97% after 5000 cycles, showing its prospects as a commercial ASC electrode.

Nanocomposites of Nitrogen-Doped Graphene Oxide and Manganese Oxide for Photodynamic Therapy and Magnetic Resonance Imaging.

Cancer is a leading cause of death worldwide. Conventional methods of cancer treatment, including chemotherapy and radiotherapy, are associated with multiple side effects. Recently, photodynamic therapy (PDT) has emerged as an effective therapeutic modality for cancer treatment without adversely affecting normal tissue. In this study, we synthesized nitrogen doped graphene (NDG) and conjugated it with Mn3O4 nanoparticles to produce NDG-Mn3O4 nanocomposite with the aim of testing its bimodal performance including PDT and magnetic resonance imaging (MRI). We did not use any linker or binder for conjugation between NDG and Mn3O4, rather they were anchored by a milling process. The results of cell viability analysis showed that NDG-Mn3O4 nanocomposites caused significant cell death under laser irradiation, while control and Mn3O4 nanoparticles showed negligible cell death. We observed increased generation of singlet oxygen after exposure of NDG-Mn3O4 nanocomposites, which was directly proportional to the duration of laser irradiation. The results of MRI showed concentration dependent enhancement of signal intensity with an increasing concentration of NDG-Mn3O4 nanocomposites. In conclusion, NDG-Mn3O4 nanocomposites did not cause any cytotoxicity under physiological conditions. However, they produced significant and dose-dependent cytotoxicity in cancer cells after laser irradiation. NDG-Mn3O4 nanocomposites also exhibited concentration-dependent MRI contrast property, suggesting their possible application for cancer imaging. Further studies are warranted to test the theranostic potential of NDG-Mn3O4 nanocomposites using animal models of cancer.

Botulinum toxin A for the treatment of first bite syndrome-a systematic review.

Background: First bite syndrome (FBS) is a rare post-surgical complication resulting in peri-parotid pain after the first bite of meals. Intra-parotid Botulinum toxin A may offer relief for these symptoms. There is no consensus on the optimal dosage, timing to symptom improvement, need for repeat injections, and safety of this treatment. The objective of this systematic review was to assess the efficacy and safety of intra-parotid Botulinum toxin A injection in treating FBS. Methods: The MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar were searched from the inception until July 2020. Case reports, case series, prospective and retrospective trials in which patients with post-surgical FBS were treated with intra-parotid botulinum toxin A injection were included. The primary outcome was improvement of FBS symptoms. Secondary outcomes were time to symptom improvement and complications. Risk of bias was assessed with National Institute of Health (NIH) Quality Assessment Tools. Results: Search results yielded 41 studies. Thirty-three articles were excluded after screening titles, abstracts, and full texts, yielding eight studies, from which 22 patients were included. No studies included a control. All studies were of lower quality and had at least moderate risk of bias. The initial botulinum toxin A injection dose ranged from 10-75 U. Time from surgical treatment to injection ranged from 1 month to 3 years. Seven studies, containing 17 patients, reported individual patient outcomes. Clinical improvement was reported in 16 patients lasting between 1-30 months post injection. Eight of 8 (100%) patients receiving at least 40 U botulinum toxin A had symptom improvement. Ten of 22 (45.5%) patients received a second botulinum toxin A injection due to return of pain at a mean of 3.8 months after the first injection. Seven of 22 (38.1%) patients had complete symptom resolution at a mean of 12.1 months. There were no reported injection complications, including: facial paralysis, infection, injection site reaction, and allergic reaction. Discussion: There are no controlled studies comparing intra-parotid botulinum toxin A to observation for FBS. However, botulinum toxin A appears to be a potentially safe, effective treatment.

Frequency, distribution and determinants of Helicobacter pylori infection in adults and adolescents with gastric symptoms: cross-sectional epidemiological inquiry in district Haripur, Pakistan.

Helicobacter pylori (HP) is a vital element in the etiology of peptic ulcers and gastric cancer. This research aimed to determine the frequency, distribution, and determinants of HP infection in adults and adolescents with gastric symptoms in district Haripur, Khyber Pakhtunkhwa, Pakistan. This cross-sectional study was performed from June 2018 to June 2020 at the Medical Laboratory Technology Department, The University of Haripur, Pakistan. Presence of HP was a research variable, while sex, age groups, education status, overcrowding, dining habits, milk intake, drinking water source and animal contact were grouping variables. Immuno-chromatographic technique (ICT) was used to for serological detection of HP antibodies. All variables were represented by frequency and percentage with 95%CI. Prevalence of HP and its distribution by eight socio-demographic variables was testified by the chi-square goodness-of-fit test while association was testified by chi-square test of association. Out of total 1160 cases, 557 (48%) were positive for HP. Population prevalence was higher in men, in the age group 20-40 years, illiterate, family size ≤ 10 persons, taking restaurant food, using tetra pack, using municipal water, and having animal contact. The observed prevalence of HP was similar to its expected prevalence in the population. The observed distribution of HP in the sample was different from its expected distribution in population by eight socio-demographic variables. Presence of HP was associated with all eight socio-demographic variables besides age groups.

Phytochemical Profiling of Microalgae Euglena tuba and Its Anticancer Activity in Dalton's Lymphoma Cells.

INTRODUCTION: Natural phytochemicals are considered safe to use as therapeutic agents. There is a growing trend toward exploring anticancer effects of crude algal extracts or their active ingredients. Euglena tuba, a microalga, contains excellent antioxidant potential. However, the anticancer property of E. tuba has not been explored. This study investigates the chemical profiling as well as antitumor property of methanolic extract of E. tuba (ETME) against Dalton's lymphoma (DL) cells. MATERIALS AND METHODS: E. tuba, procured from northern part of India, was extracted in 70% methanol, dried at room temperature, and stored at -20 ∘C for future use. A freshly prepared aqueous solution of ETME of different concentrations was employed into each experiment. The ETME mediated anti-tumor response in Dalton's lymphoma was evaluated in the inbred populations of BALB/c (H2d) strain of mice of either sex at 8-12 weeks of age. The cytotoxicity of ETME in cancer cells, effects on morphology of cell and nucleus, alteration in the mitochondrial membrane potential, and level of expression of proapoptotic proteins (Bcl-2, cyt C, Bax and p53) were done using known procedures. RESULTS: The ETME contained high content of total alkaloids (96.02 ± 3.30 mg/100 mg), flavonoids (15.77 ± 2.38 mg/100 mg), carbohydrate (12.71 ± 0.59 mg/100 mg), ascorbic acid (12.48 ± 2.59 mg/100 mg), and phenolics (0.94 ± 0.05 mg/100 mg). Gas chromatography-mass spectrometry (GC-MS) analysis indicated the presence of 23 phytochemicals with known anticancer properties. DL cells treated with ETME exhibited significant and concentration dependent cytotoxicity. Florescent microscopy and flow cytometry of ETME treated DL cells indicated significant repair in cellular morphology and decreased mitochondrial potential, respectively. Western blot analysis displayed up-regulation of proapoptotic proteins (Bax, Cyt-c, p53) and down regulation of anti-apoptotic protein (Bcl2) in DL cells treated with ETME. CONCLUSIONS: The findings of this study clearly indicated that the anticancer property of ETME was mediated via reduction in mitochondrial potential and induction of apoptotic mechanism. Further studies are warranted to explore the anticancer activities of active ingredients present in this microalga of pharmaceutical importance.

Association between preventable risk factors and metabolic syndrome.

The risk factors associated with metabolic syndrome (Met-S) including hypertension, hyperglycemia, central obesity, and dyslipidemia are preventable, particularly at their early stage. There are limited data available on the association between Met-S and preventable risk factors in young adults. We randomly selected 2,010 Saudis aged 18-30 years, who applied to be recruited in military colleges. All the procedures followed the guidelines of International Diabetes Federation. The results showed that out of 2,010 subjects, 4088 were affected with Met-S. The commonest risk factors were high blood sugar (63.6%), high systolic and diastolic blood pressures (63.3 and 37.3%), and high body mass index (57.5%). The prevalence of prediabetes and diabetes were 55.2 and 8.4%, respectively. Obesity, diabetes, hypertension, and hypertriglyceridemia were significantly associated with Met-S. The frequency of smoking was significantly linked with the development of Met-S. The prevalence of Met-S was found to be significantly higher in individuals with sedentary lifestyle. In conclusion, the results of this study clearly indicate that military recruits, who represent healthy young adults, are also prone to Met-S. The findings of this study will help in designing preventive measures as well as public awareness programs for controlling the high prevalence of Met-S in young adults.

Cellular antioxidant potential and inhibition of foodborne pathogens by a sesquiterpene ilimaquinone in cold storaged ground chicken and under temperature-abuse condition.

A sesquiterpene quinone, ilimaquinone, was accessed for its cellular antioxidant efficacy and possible antimicrobial mechanism of action against foodborne pathogens (Staphylococcus aureus and Escherichia coli) in vitro and in vivo. Ilimaquinone was found to be protective against H2O2-induced oxidative stress as validated by the reduction in the ROS levels, including increasing expression of SOD1 and SOD2 enzymes. Furthermore, ilimaquinone evoked MIC against S. aureus and E. coli within the range of 125-250 µg/mL. Ilimaquinone established its antimicrobial mode of action against both tested pathogens as evident by bacterial membrane depolarization, loss of nuclear genetic material, potassium ion, and release of extracellular ATP, as well as compromised membrane permeabilization and cellular component damage. Also, ilimaquinone showed no teratogenic effect against zebrafish, suggesting its nontoxic nature. Moreover, ilimaquinone significantly reduced the S. aureus count without affecting the sensory properties and color values of cold-storaged ground chicken meat even under temperature abuse condition.

Relapse of Psychosis Status Post Meningioma Resection.

A 53-year-old Caucasian female with a previous psychiatric history of bipolar I disorder and attention deficit hyperactivity disorder presented to the emergency department after endorsing 10-11 months of auditory and visual hallucinations, persecutory delusions, depression, anosmia, weakness of lower extremities, and headache. The patient described her auditory hallucinations as non-commanding voices talking to her about her family, her visual hallucinations as seeing "shadows and shapes," and her paranoid delusions as people coming after her. The patient had sustained a fall a week and a half earlier, requiring eight sutures to her posterior scalp. Her MRI of the brain showed a well-circumscribed 3.5 x 4.7 x 3.2 cm mass in the floor of the anterior cranial fossa. Computer tomography of the brain showed a 4.5 cm mass near the anterior interhemispheric fissure and edema in the right frontal cortex. Meningioma resection resulted in the cessation of hallucinations and delusions for one week. However, the patient was brought back to the emergency department because her auditory hallucinations and delusions returned. This case report demonstrates residual psychosis, even after frontal meningioma resection.

Pro-Apoptotic and Immunotherapeutic Effects of Carbon Nanotubes Functionalized with Recombinant Human Surfactant Protein D on Leukemic Cells.

Nanoparticles are efficient drug delivery vehicles for targeting specific organs as well as systemic therapy for a range of diseases, including cancer. However, their interaction with the immune system offers an intriguing challenge. Due to the unique physico-chemical properties, carbon nanotubes (CNTs) are considered as nanocarriers of considerable interest in cancer diagnosis and therapy. CNTs, as a promising nanomaterial, are capable of both detecting as well as delivering drugs or small therapeutic molecules to tumour cells. In this study, we coupled a recombinant fragment of human surfactant protein D (rfhSP-D) with carboxymethyl-cellulose (CMC) CNTs (CMC-CNT, 10-20 nm diameter) for augmenting their apoptotic and immunotherapeutic properties using two leukemic cell lines. The cell viability of AML14.3D10 or K562 cancer cell lines was reduced when cultured with CMC-mwCNT-coupled-rfhSP-D (CNT + rfhSP-D) at 24 h. Increased levels of caspase 3, 7 and cleaved caspase 9 in CNT + rfhSP-D treated AML14.3D10 and K562 cells suggested an involvement of an intrinsic pathway of apoptosis. CNT + rfhSP-D treated leukemic cells also showed higher mRNA expression of p53 and cell cycle inhibitors (p21 and p27). This suggested a likely reduction in cdc2-cyclin B1, causing G2/M cell cycle arrest and p53-dependent apoptosis in AML14.3D10 cells, while p53-independent mechanisms appeared to be in operation in K562 cells. We suggest that CNT + rfhSP-D has therapeutic potential in targeting leukemic cells, irrespective of their p53 status, and thus, it is worth setting up pre-clinical trials in animal models.

Selective Serotonin Reuptake Inhibitors and Adverse Effects: A Narrative Review.

Depression is the most prevalent psychiatric disorder in the world, affecting 4.4% of the global population. Despite an array of treatment modalities, depressive disorders remain difficult to manage due to many factors. Beginning with the introduction of fluoxetine to the United States in 1988, selective serotonin reuptake inhibitors (SSRIs) quickly became a mainstay of treatment for a variety of psychiatric disorders. The primary mechanism of action of SSRIs is to inhibit presynaptic reuptake of serotonin at the serotonin transporter, subsequently increasing serotonin at the postsynaptic membrane in the serotonergic synapse. The six major SSRIs that are marketed in the USA today, fluoxetine, citalopram, escitalopram, paroxetine, sertraline, and fluvoxamine, are a group of structurally unrelated molecules that share a similar mechanism of action. While their primary mechanism of action is similar, each SSRI has unique pharmacokinetics, pharmacodynamics, and side effect profile. One of the more controversial adverse effects of SSRIs is the black box warning for increased risk of suicidality in children and young adults aged 18-24. There is a lack of understanding of the complexities and interactions between SSRIs in the developing brain of a young person with depression. Adults, who do not have certain risk factors, which could be confounding factors, do not seem to carry this increased risk of suicidality. Ultimately, when prescribing SSRIs to any patient, a risk-benefit analysis must factor in the potential treatment effects, adverse effects, and dangers of the illness to be treated. The aim of this review is to educate clinicians on potential adverse effects of SSRIs.

In-situ study of electrochemical migration of tin in the presence of bromide ion.

The miniaturization of electronic devices and the consequent decrease in the distance between conductive lines have increased the risk of short circuit failure due to electrochemical migration (ECM). The presence of ionic contaminants affects the ECM process. This work systematically investigates the ECM of tin (Sn) in the presence of bromide ions (Br-) in the range of 10-6 M to 1.0 M. Water drop test (WDT) was conducted in the two-probe semiconductor characterization system under an optical microscope as an in-situ observation. Polarization test was carried out to study the correlation between the corrosion properties of Sn and its ECM behaviour. The products of ECM were characterized by scanning electron microscope coupled with an energy dispersive X-rays spectrometer (SEM/EDX) and X-ray photoelectron spectrometer (XPS). The results confirm that the rate of anodic dissolution of Sn monotonously increases with the Br- concentration. However, the probability of ECM failure follows a normal distribution initially, but later increases with the Br- concentration. The main products of the ECM reactions are identified as Sn dendrites and tin hydroxide precipitates. The mechanisms of the ECM process of Sn in the presence of Br- are also suggested.

Growth of 1D TiO2nanostructures on Ti substrates incorporated with residual stress through humid oxidation and their characterizations.

Different Ti substrates, such as particles (as-received and ball milled), plate and TEM grid were oxidized for the growth of one dimensional (1D) TiO2nanostructures. The Ti substrates were oxidized for 4 h at temperatures of 700 °C-750 °C in humid and dry Ar containing 5 ppm of O2. The effects of residual stress on the growth of 1D TiO2nanostructures were investigated. The residual stress inside the Ti particles was measured by XRD-sin2ψtechnique. The oxidized Ti substrates were characterized using field emission scanning electron microscope equipped with energy dispersive x-ray spectroscope, transmission electron microscope, x-ray diffractometer and x-ray photoelectron spectroscope. Results revealed that humid environment enhances the growth of 1D TiO2nanostructures. Four different types of 1D morphologies obtained during humid oxidation, e.g. stacked, ribbon, plateau and lamp-post shaped nanostructures. The presence of residual stress significantly enhances the density and coverage of 1D nanostructures. The as-grown TiO2nanostructures possess tetragonal rutile structure having length up to 10µm along the 〈1 0 1〉 directions. During initial stage of oxidation, a TiO2layer is formed on Ti substrate. Lower valence oxides (Ti3O5, Ti2O3and TiO) then form underneath the TiO2layer and induce stress at the interface of oxide layers. The induced stress plays significant role on the growth of 1D TiO2nanostructures. The induced stress is relaxed by creating new surfaces in the form of 1D TiO2nanostructures. A diffusion based model is proposed to explain the mechanism of 1D TiO2growth during humid oxidation of Ti. The 1D TiO2nanostructures and TiO2layer is formed by the interstitial diffusion of Ti4+ions to the surface and reacts with the surface adsorbed hydroxide ions (OH-). Lower valence oxides are formed at the metal-oxide interface by the reaction between diffused oxygen ions and Ti ions.

Phytochemicals reverse P-glycoprotein mediated multidrug resistance via signal transduction pathways.

P-glycoprotein, encoded by ATP-binding cassette transporters B1 gene (ABCB1), renders multidrug resistance (MDR) during cancer chemotherapy. Several synthetic small molecule inhibitors affect P-glycoprotein (P-gp) transport function in MDR tumor cells. However, inhibition of P-gp transport function adversely accumulates chemotherapeutic drugs in non-target normal tissues. Moreover, most small-molecule P-gp inhibitors failed in the clinical trials due to the low therapeutic window at the maximum tolerated dose. Therefore, downregulation of ABCB1-gene expression (P-gp) in tumor tissues seems to be a novel approach rather than inhibiting its transport function for the reversal of multidrug resistance (MDR). Several plant-derived phytochemicals modulate various signal transduction pathways and inhibit translocation of transcription factors, thereby reverses P-gp mediated MDR in tumor cells. Therefore, phytochemicals may be considered an alternative to synthetic small molecule P-gp inhibitors for the reversal of MDR in cancer cells. This review discussed the role of natural phytochemicals that modulate ABCB1 expression through various signal transduction pathways in MDR cancer cells. Therefore, modulating the cell signaling pathways by phytochemicals might play crucial roles in modulating ABCB1 gene expression and the reversal of MDR.