Regulating Social Media in the Global South

In recent years, the disinformation crisis has made regulating social media platforms a necessity. The consequences of disinformation campaigns are not only limited to election interferences or political debates, but have also included fatal consequences. In response, scholars have generally focused on regulating social media companies in the United States without paying much attention to these companies’ global impact, particularly in the Global South. Lost in the quest to fight disinformation is addressing the social media companies’ neglect of consumer rights in the Global South. Countries in the Global North, such as the United States, have the power to regulate social media companies should they choose to do so. However, the current power asymmetry between major social media companies and countries in the Global South limits the ability of many of such countries to have any meaningful bargaining power to advocate for their citizens’ consumer rights and their ability to manage misinformation campaigns in their sovereign territories. In some countries, it is even unclear if there is any political will from their respective government to advocate for consumer rights. This problem will not be resolved by relying on corporate social responsibility or corporate self-governance. Thus, this Article argues that unless countries in the Global South act collectively, they should not expect any major change from powerful social media companies in handling misinformation in their countries or promoting their citizens’ consumer rights. Regional treaties among countries, as a form of collective action, could push social media companies to be more attentive to their actions outside the Global North and bear responsibility in a transnational space. Ultimately, collective action in the Global South could inspire a global coalition and promote global accountability

DECELLULARIZATION OF LUNG TISSUE AND ANALYSIS OF ITS DIFFERENTIATIVE POTENTIAL ON BONE MARROW MESENCHYMAL STEM CELLS OF RAT

Background: Pulmonary diseases are one of the most common causes of mortality worldwide. In some cases lung transplantation is the only curative treatment. Unfortunately, very few lungs are available for transplantation and also the 5-year survival after lung transplantation is only 50%. Furthermore, transplant recipients require immunosuppressant therapy in that’s time. Currently, production of engineered lung tissue using in vitro stem cells is a promising approach. Extraction of natural ECM or decellularization of lung and application of it in tissue engineering is one of the most important strategies in this regard. Using this technique can preserve the natural characteristics of the ECM and would leads to the removal of the immunogen agents (MHC I, II) and allows reconstruction of graft. Objective: In this study we have decellularized rat lung and cultured bone marrow stem cells on it to evaluate differentiative potential of it. Methods: In this study along with extraction of rat lung, its femur and tibia bones were also isolated for extraction of mesenchymal stem cells. Lung tissue was decellularized using SDS detergent. SEM and H&E staining used to assay decellularization. Finally mesenchymal stem cells were seed on the decellularized tissue sections and immunocytochemistry for CC10 and SPD; as markers for differentiation toward lung cells, performed on these cells after 21 days. Results:In the H&E slides of decellularized tissue there were not any cells. In the electron microscope images of decellularized tissue compared with normal tissue, alveolar structure was well maintained. Also, immunocytochemistry assay showed evidence of differentiation of seeded mesenchymal cells toward lung tissue cells. Conclusion:In this method decellularization take place without any significant change in tissue structure. Decellularized tissue can induce differentiation of bone marrow stem cells toward lung epithelial cells so natural ECM saved relatively

CRISPR/Cas9-mediated knockout of MLL5 enhances apoptotic effect of cisplatin in HeLa cells in vitro

Mixed lineage leukemia 5 (MLL5) transactivates the expression of E6 and E7 oncogenes in cervical cancer cells. In this study, we utilized ‎CRISPR/Cas9 system with the aim to target HPV-E6 and MLL5 to enhance apoptosis efficiency in HPV-18 positive HeLa cells and to improve chemotherapeutic efficacy of Cisplatin as the most common anticancer drug, used for cervical cancer. ‎sgRNAs against MLL5 and E6 were designed and cloned into PX458 plasmid vector. ‎Real-time ‎PCR was used to determine knockout expression of MLL5 and E6 following, ‎transfection with cloned plasmids. Cell viability and apoptosis were evaluated, using ‎Dimethyl-thiazolyl diphenyl tetrazolium bromide (MTT) ‎assay and Annexin V flow cytometry. ‎‏Cellular p‎53 level was measured, using enzyme linked immune sorbent assay (ELISA).‏ Real-time ‎PCR indicated the downregulation of E6 and MLL5 in the transfected cells. ‎A significant increase in the accumulation of P53 was observed due to targeting MLL5 and E6 genes. MTT and ‎apoptosis assays showed a significant decrease in cell viability and enhanced apoptosis rate of ‎transfected cells. Combination therapy showed that targeting E6 and MLL5 enhanced ‎apoptotic effect of Cisplatin in MLL5 knockout cells in a synergistic manner. ‎‏The results suggest that CRISPR/Cas9 targeting of E6 and MLL5 genes can increase‎ apoptotic effects of Cisplatin and can be considered as a ‎‎potential combination therapy for the treatment of HPV-‎related cervical cancer.

Effects of Two-by-Two Combination Therapy with Valproic Acid, Lithium Chloride, and Celecoxib on the Angiogenesis of the Chicken Chorioallantoic Membrane

Background: The synergistic effects of valproic acid (VPA), lithium (Li), and celecoxib (CX) have been shown in combination therapy against the proliferation and metastasis of numerous cancers. Angiogenesis plays a critical role in the pathogenesis of tumor growth and metastasis. The aim of the present study was to evaluate the antiangiogenic effects of VPA, lithium chloride (LiCl), and CX, alone or in 2-by-2 combinations, using the chicken chorioallantoic membrane (CAM) assay. Methods: Fertilized chicken eggs were randomly divided into 10 groups: control, VPA (1.8 and 3.6 µmol/CAM), Li (0.15 and 0.60 µmol/CAM), CX (0.02 and 0.08 µmol/CAM), VPA+Li, VPA+CX, and CX+Li (n=10 per group). A window was made on the eggshells and the CAMs were exposed to a filter disk containing VPA, LiCl, and CX, alone or in 2-by-2 combinations. The control CAMs were treated with distilled water (vehicle). Three days after the treatment, the number of vessel branch points was counted in each CAM. The data were analyzed using SPSS, version 15.One-way ANOVA, followed by the Tukey tests, was used to compare the groups. A P<0.05 was considered a statistically significant difference between the groups. Results: According to the results, all the tested drugs decreased the number of the vessel branch points in a dose-dependent manner compared to the control group (P<0.001). In addition, combinations of the drugs were more effective in decreasing angiogenesis than the use of each drug alone. Conclusion: These findings suggest that 2-by-2 combinations of VPA, CX, and LiCl can be considered an effective antiangiogenesis therapeutic modality

Update on the pharmacology of calcitonin/CGRP family of peptides:IUPHAR Review 25

The calcitonin/calcitonin gene-related peptide (CGRP) family of peptides includes calcitonin, α and β CGRP, amylin, adrenomedullin (AM) and adrenomedullin 2/intermedin (AM2/IMD). Their receptors consist of one of two G protein-coupled receptors (GPCRs), the calcitonin receptor (CTR) or the calcitonin receptor-like receptor (CLR). Further diversity arises from heterodimerisation of these GPCRs with one of three receptor activity-modifying proteins (RAMPs). This gives the CGRP receptor (CLR/RAMP1), the AM1 and AM2 receptors (CLR/RAMP2 or RAMP3) and the AMY1, AMY2 and AMY3 receptors (CTR/RAMPs1-3 complexes, respectively). Apart from the CGRP receptor, there are only peptide antagonists widely available for these receptors and these have limited selectivity, thus defining the function of each receptor in vivo remains challenging. Further challenges arise from the probable co-expression of CTR with the CTR/RAMP complexes and species-dependent splice variants of the CTR (CT(a) and CT(b)). Furthermore, the AMY1(a) receptor is activated equally well by both amylin and CGRP and the preferred receptor for AM2/IMD has been unclear. However, there are clear therapeutic rationales for developing agents against the various receptors for these peptides. For example many agents targeting the CGRP system are in clinical trials and pramlintide, an amylin analogue, is an approved therapy for insulin-requiring diabetes. This review provides an update on the pharmacology of the calcitonin family of peptides by members of the corresponding subcommittee of the International Union of Basic and Clinical Pharmacology and colleagues

Kidney, Money, and the Shī‘ah Implementation of the Rule of Necessity

In the U.S., over 43,000 people die every year waiting for a kidney. In Iran, however, monetary incentives have eliminated such a waitlist. Iran is the only country in the world with an unrelated living kidney donor program that has allowed for monetary incentives in the form of an altruistic gift, which has become known as the "Iranian Mode." Nevertheless, the legal details of the system remain vague and scholars both in and outside of Iran continue to debate the nature of the system. Does the Iranian system consider kidneys a commodity? Can you legally buy a kidney in Iran? If not, what is the legal nature of the monetary incentive? The answers to these questions are particularly important as many countries seek to find the right approach in addressing kidney shortages. This Article follows the newly established guidelines of the Iranian Model and seeks to answer these questions. It argues that Iran's peculiarity is neither related to its view on the marketability of the kidney nor the proprietary nature of the organ; instead, it can be associated with the principle of of necessity as interpreted by&nbsp;Shī‘ah Islam in Iran. The legal nature of the act of giving monetary incentives is also best described under the Islamic contract of&nbsp;ju’ala—the unilateral contract of reward. This Model as explained in this article can be implemented outside of Iran, eliminating the need to create a market for the sale of kidneys as some scholars have suggested

Protective effects of nimodipine and lithium against aluminum-induced cell death and oxidative stress in PC12 cells

Objective(s): The role of aluminum (Al) in the pathogenesis of neurodegenerative diseases has been implicated in several studies. However, the exact mechanisms of cytotoxic effects of Al have not been elucidated yet. The aim of this study was to investigate the effect of L-type calcium channel antagonist, nimodipine (NM), and lithium chloride (LiCl) on Al-induced toxicity in PC12 cells. Materials and Methods: PC12 cells were treated with Al-maltolate (Almal) in the presence and absence of different concentrations of NM (50-150 μm) and/or LiCl (0.5-1.0 mm) for 48 hr. Cell viability, apoptosis, and catalase (CAT) activity, a marker of oxidative stress, were then measured using MTT, flow cytometry and enzyme assay, respectively. Results: The results showed that Almal, dose dependently induced cell death, apoptosis and CAT activity in the PC12 cells. NM significantly increased cell viability and decreased apoptosis and CAT activity of Almal-treated cells in a dose dependent mode. LiCl reduced CAT activity and increased cell viability in Almal-treated cells, without significant effect on apoptosis (P=0.74). Conclusion: These findings suggest that NM and Li may have benefits in the prevention of Al-induced cytotoxicity through decreasing oxidative stress