The Safety and Efficacy of Mesenchymal Stem Cells in the Treatment of Type 2 Diabetes- A Literature Review.

Introduction: Type 2 diabetes (T2D) is the most common type of diabetes, affecting 6.28% of the population worldwide. Over the decades, multiple therapies and drugs have been developed to control T2D, but they are far from a long-term solution. Stem cells are promising as novel regenerative treatments, especially mesenchymal stem cells (MSCs), which are highly versatile in their regenerative and paracrine capabilities and characteristics. This makes them the most commonly used adult stem cells and ideal candidates to treat diabetes. Objective: To assess the safety and efficacy of mesenchymal stem cells (MSCs) in treating Type 2 diabetes (T2D) in humans. Methods: Mesenchymal stem cell-based treatments were studied in 262 patients. A total of 6 out of 58 trials fit our inclusion criteria in the last five years. Results: The treatment of patients with MSCs reduced the dosage of anti-diabetic drugs analyzed over a follow-up period of 12 months. The effective therapy dosage ranged from 1×106 cells/kg to 3.7×106 cells/kg. After treatment, HbAc1 levels were reduced by an average of 32%, and the fasting blood glucose levels were reduced to an average of 45%. The C-peptide levels were decreased by an average of 38% in 2 trials and increased by 36% in 4 trials. No severe adverse events were noted in all trials. Conclusion: This analysis concludes that MSC treatment of type 2 diabetes is safe and effective. A larger sample size is required, and the trials should also study the effect of differentiated MSCs as insulin-producing cells.

Mutational heterogeneity in spike glycoproteins of severe acute respiratory syndrome coronavirus 2.

The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has led to a global crisis by infecting millions of people across the globe eventually causing multiple deaths. The prominent player of the virus has been known as the spike protein which enters the host system and leads to the infection. The S2 subunit is the most essential in this process of infection as it helps the SARS-CoV-2 to infect the host by binding to the human angiotensin converting enzyme 2 (hACE2), with the help of the receptor binding domain found at the S2 subunit of the virus. Studies also hypothesize that the S glycoproteins present in the virus interacts with different hosts in different ways which might be due to the mutations taking place in the genome of the virus over time. This work aims to decipher the similarities and differences in the sequences of spike proteins from samples of SARS-CoV-2 acquired from different infected individuals in different countries with the help of in silico methods such as multiple sequence alignment and phylogenetic analysis. It also aims to understand the differential infection rates among the infected countries by studying the amino acid composition and interactions of the virus with the host.

Curcumin⁻Copper Complex Nanoparticles for the Management of Triple-Negative Breast Cancer.

Breast cancer is the most common cancer diagnosed among females worldwide. Although breast cancer survival has largely improved in the past 30 years, it remains highly heterogeneous in its response to treatment. Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks the expression of the estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor-2 (Her2). While TNBC may initially be responsive to chemotherapy, recurrence and subsequent high mortality rates are frequently reported. Studies have shown curcumin and its derivatives to be effective against TNBC cell lines in vitro. To improve its anti-cancer effects, we have synthesized Fe3+⁻curcumin (Fe⁻Cur3) and Cu2+⁻curcumin (CD) complexes and investigated them experimentally. Further, CD was encapsulated into a poly(styrene)-co-maleic acid (SMA) micelle to enhance its stability. We assessed the cytotoxicity of these formulations both in vitro and in vivo. SMA⁻CD demonstrated dose-dependent cytotoxicity and abolished TNBC tumor growth in vivo. The encapsulation of the curcumin⁻copper complex improved its anti-cancer activity without overt adverse effects in a murine model of TNBC. These results provide evidence and insights into the value of nanoformulations in enhancing drug-delivery and increasing the potential therapeutic efficacy of curcumin derivatives.

Synthetic cannabinoids nano-micelles for the management of triple negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with poor prognosis and inadequate therapeutic outcome. This contribution reports the use of a cannabinoid derivative, WIN55,212-2 (WIN) on the growth of TNBC in a 4T1 syngeneic mouse model. To reduce the well-known psychoactive side effects of cannabinoids, we prepared a nanomicellar formulation of WIN (SMA-WIN). In vivo biodistribution, in silico ADME predictions, anticancer activity, and psychoactive effect of WIN and SMA-WIN studies suggest that SMA-WIN formulation can reduce to greater extent tumor growth with milder psychoactive side effects when compared to free drug. Finally, the effects of WIN and SMA-WIN in combination with doxorubicin (Doxo), an established chemotherapeutic agent for the treatment of TNBC, were investigated in vitro and in vivo. SMA-WIN in combination with Doxo showed therapeutic efficacy and was able to reduce the tumor volume of TNBC murine model drastically. Moreover, SMA-WIN, while favoring drug tumor accumulation, minimized the adverse psychoactive effects that have impeded the use of this agent in the clinic. To our knowledge, this is the first report for the assessment of cannabinoid nanoparticles in vivo for the treatment of TNBC and its enhanced anticancer effect at low doses with Doxo. These findings suggest a new therapeutic strategy in the management of TNBC.

Nanomedicine: is it lost in translation?

By the end of 2017 more than 200,000 scientific research articles had been published about nanomedicine. Out of this vast number only a few of the reported nanoconstructs reached clinical trials for various applications, including the diagnosis and treatment of several cancers, and the treatment of infections and other non-cancerous diseases. 30 years after the pioneering work in this field of research, the low product yield at the end of research pipeline leads to a question that is asked by many: 'had nanomedicine been lost in translation?' In this review, we will discuss the landscape of nanomedicine regarding cancer treatment and miscellaneous applications as well as some obstacles toward full utilization of this powerful therapeutic tool and suggest a few solutions to improve the current translational value of nanomedicine research.