Pharmacological Management of Tuberculosis, Challenges, and Potential Strategies

Tuberculosis (TB) is an infection caused by the pathogen Mycobacterium tuberculosis. The disease causes around 2 million deaths worldwide, and incidences of drug resistance only makes increases the number. The most vulnerable victims of TB infections are children and human immunodeficiency virus (HIV) patients. TB and HIV co-infections can be deadly in AIDS sufferers, as the immune system is not able to combat TB infections, hence worsening the infection. Common drugs to treat TB are available in the market, first-line drugs such as isoniazid and rifamycin are broad-spectrum drugs. Second-line antibiotics such as fluoroquinolones are also available. In this review, the mechanisms of action of TB drugs are briefly discussed, as wells as the respective resistant mechanisms of M. tuberculosis against these drugs. An updated treatment regime for TB management using bedaquiline, pretomanid and linezolid was also discussed, which shows 90% therapeutic efficacy against highly drug-resistant tuberculosis cases. Furthermore, novel strategies such as nanoparticle-conjugated TB drugs can improve drug delivery, TB drug efficiency while reducing side effects. However, importance on patient compliance to the treatment regime is still the most crucial part of TB management, hence initiatives can be put to improve patient awareness and education

Matrix metalloproteinases in chemoresistance: regulatory roles, molecular interactions, and potential inhibitors

Cancer is one of the major causes of death worldwide. Its treatments usually fail when the tumor has become malignant and metastasized. Metastasis is a key source of cancer recurrence, which often leads to resistance towards chemotherapeutic agents. Hence, most cancer-related deaths are linked to the occurrence of chemoresistance. Although chemoresistance can emerge through a multitude of mechanisms, chemoresistance and metastasis share a similar pathway, which is an epithelial-to-mesenchymal transition (EMT). Matrix metalloproteinases (MMPs), a class of zinc and calcium-chelated enzymes, are found to be key players in driving cancer migration and metastasis through EMT induction. The aim of this review is to discuss the regulatory roles and associated molecular mechanisms of specific MMPs in regulating chemoresistance, particularly EMT initiation and resistance to apoptosis. A brief presentation on their potential diagnostic and prognostic values was also deciphered. It also aimed to describe existing MMP inhibitors and the potential of utilizing other strategies to inhibit MMPs to reduce chemoresistance, such as upstream inhibition of MMP expressions and MMP-responsive nanomaterials to deliver drugs as well as epigenetic regulations. Hence, manipulation of MMP expression can be a powerful tool to aid in treating patients with chemo-resistant cancers. However, much still needs to be done to bring the solution from bench to bedside