Simultaneous estimation of paclitaxel and bortezomib via LC-MS/MS: pharmaceutical and pharmacokinetic applications.

Aim & Objective: This study evaluates the potential of combining paclitaxel (PTX) and bortezomib (BTZ) for breast cancer therapy.Materials & Methods: The nanoformulation was optimized via Box-Behnken Design (BBD), with method validation adhering to US-FDA guidelines.Results: Multiple reaction monitoring transitions for PTX, BTZ and internal standard were m/z 855.80→286.60, 366.80→226.00 and 179.80→110.00, respectively. Elution done on C18 Luna column with 0.1% FA in MeOH:10 mM ammonium acetate. The size of nanoformulation was 133.9 ± 1.97 nm, PDI 0.19 ± 0.01 and zeta potential -19.20 ± 1.36 mV. Pharmacokinetics showed higher Cmax for PTX-BTZ-NE (313.75 ± 10.71 ng/ml PTX, 11.92 ± 0.53 ng/ml BTZ) versus free PTX-BTZ (104 ± 13.06 ng/ml PTX, 1.9 ± 0.08 ng/ml BTZ).Conclusion: Future findings will contribute to the treatment of breast cancer using PTX and BTZ.

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In-silico and in-vivo evaluation of sesamol and its derivatives for benign prostatic hypertrophy.

Pharmacological treatment for BPH includes 5-α reductase inhibitors as Finasteride and Dutasteride as a monotherapy or in combination with antimuscarinic drugs, alpha-blockers, 5-phosphodiesterase inhibitor drugs. Androgen receptor inhibitors revealed several adverse events as decreased libido, erectile dysfunction, ejaculatory dysfunction, and gynecomastia. Hence, the emergence of complementary and alternative medications having safety profile-preferably, edible natural products-would be highly desirable. In-silico studies based on Maestro Molecular Modelling platform (version 10.5) by SchrÓ§dinger, LLC was used to identify the lead molecules. The in-vivo activity studied on rats gave the positive results. The findings based on experiments as antioxidant parameters showed the potential to quench the free radicals. The significant results were also seen in prostatic index and histopathological studies supported the above findings. Based on these data, sesamol and derivative have proven efficacy in protecting against testosterone induced BPH. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02952-z.

Mechanistic targets for BPH and prostate cancer-a review.

All men, almost, suffer from prostatic disorders in average life expectancy. In the year of 1950s, the first autopsy of prostate gland discovered the link between Benign prostatic hyperplasia (BPH) and Prostate Cancer (PCa). After that, many histology, biochemistry, epidemiology studies explained the association and associated risk factor for the same. From the various scientific evidence, it is proved that both diseases share some common transcription factors and signalling pathways. Still, BPH cannot be considered as the first step of PCa progression. To define, the relationship between both of the diseases, a well-defined large epidemiological study is needed. Along with androgen signalling, imbalanced apoptosis, oxidative stress, and microbial infection also crucial factors that significantly affect the pathogenesis of BPH. Various signalling pathways are involved in the progression of BPH. Androgen signalling is the driving force for the progress of PCa. In PCa androgen signalling is upregulated as compared to a healthy prostate. Some dominant Androgen-regulated genes and their functions have been discussed in this work.

Histone Deacetylase Inhibitors Prevented the Development of Morphine Tolerance by Decreasing IL6 Production and Upregulating µ-Opioid Receptors.

BACKGROUND: Morphine tolerance on long-term usage leads to chronic pain conditions. Preclinical studies demonstrated that the upregulation of HDACs is associated with a decrease in the sensitivity of µ-opioid receptors, which results in morphine tolerance. OBJECTIVE: The present study was designed to assess the influence of the selected known HDAC inhibitors (NMJ2 and NMJ3) on the pain tolerance induced by chronic administration of morphine in Balb/c mice. METHODS: In the present study, morphine was administered in incremental doses 1, 2, 3.6, 6.5, 11.2, 21, and 21 mg/kg daily for seven days to develop morphine tolerance. The nociceptive thresholds, analgesia, and tolerance were assessed 30 min after morphine administration alternatively from 1st day to 7th day using the hot plate and mechanical allodynia methods. RESULTS: The morphine control group showed a reduction in the Paw Withdrawal Threshold (PWT) and the percentage Maximum Possible Effects (MPEs). In contrast, the combination of SAHA and test drugs with morphine increased the PWT and MPEs as compared to the morphine alone group. Administration of morphine alone also showed an increase in the production of the pro-inflammatory mediator, IL-6, and down-regulation of the µ-opioid receptor in the brain tissues. Treatment with HDAC inhibitors, SAHA, and test drugs showed a reversal in these changes. CONCLUSION: Results indicated that HDAC inhibitors were involved in the prevention of morphine tolerance in normal mice by inhibiting pro-inflammatory marker production and by increasing the sensitivity of neurons towards morphine in producing an analgesic effect in morphine tolerated mice.